Current
| Targeting SERCA Activation: Therapeutic Strategies for Managing Endoplasmic Reticulum Stress in Chronic Metabolic Diseases | |
| Duration: | 1. 1. 2025 - 31. 12. 2028 |
| Evidence number: | 2/0127/25 |
| Program: | VEGA |
| Project leader: | RNDr. Lomenová Jana, PhD. |
| SAS cosolvers: | Mgr. Benešová Barbora, RNDr. Kura Branislav, PhD., RNDr. Májeková Magdaléna, PhD., Ing. Micháliková Silvia, PhD., Mgr. Rezbáriková Petronela, PhD., Mgr. Wetter Erik |
| Annotation: | Calcium homeostasis imbalance activates endoplasmic reticulum (ER) stress, leading to the development of chronic metabolic diseases. The dysfunction of Sarco/Endoplasmic Reticulum Ca2+-ATPases (SERCA) has been identified as a major causative factor of ER stress. Pharmacological activation of SERCA appears to be an effective strategy in alleviating ER stress. The project will investigate the activation of SERCA by polyphenolic compounds to mitigate damage to pancreatic cells induced by methylglyoxal, palmitate, and cytokines (experimental diabetic conditions). The efficacy of compounds will be evaluated based on the activation of isolated SERCA1a protein and at the cellular level, focusing on viability, apoptosis, SERCA2b expression, insulin release, intracellular calcium levels, reactive oxygen species formation, SIRT and PPAR activation, among others. The project will contribute to clarifying the mechanisms of hyperglycemia at the cellular level and the effect of new compounds capable of mitigating ER stress. |
| Project website: | https://e-vega.sav.sk/(S(h22jztv2lbh35lvjyssbrer5))/users/Projekt_SAV_0007.aspx |
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| Duration: | 1. 1. 2025 - 31. 12. 2028 |
| Evidence number: | VEGA 2/0091/25 |
| Program: | VEGA |
| Project leader: | Mgr. Svetláková (Boťanská) Barbora, PhD. |
| ToxiGut - ToxiGut: Modeling and Prediction of Drug and Chemical Side Effects in an In Vitro 3D Reconstituted Human Small Intestine Model | |
| Duration: | 1. 1. 2025 - 31. 12. 2028 |
| Evidence number: | 2/0123/25 |
| Program: | VEGA |
| Project leader: | Dr.rer.nat., Ing. Kanďárová Helena, ERT |
| SAS cosolvers: | Mgr. Gabrišová Klara, Ing. Mahmood Sirwan Ahmed, Ing. Milasová Tatiana, Ing. Milec Lucia, Ing. Pôbiš Peter, Mgr. Pružinská-Koch Katarína, PhD, RNDr. Valachová Katarína , PhD. |
| Annotation: | The ToxiGut project proposes the development and internal validation of an advanced experimental system forstudying the side effects of chemicals and pharmaceuticals on a human 3D reconstructed model of the smallintestine. The project focuses on comparing static and dynamic methods of cultivating 3D tissue in a microfluidicdevice (Gut-on-chip concept), achieving a high level of simulation of the physiological conditions of the smallintestine. The project will compare the obtained data with experimental results from the CaCo-2 line of humancolorectal carcinoma, which is used for screening in preclinical pharmacological studies. However, this modeldoes not reflect the complexity of the human intestinal environment and, like established animal models, providesinaccurate outputs for clinical studies. The project aims to provide a more efficient testing system that will improvethe predictive ability of preclinical tests and increase the safety of patients in clinical trials while reducing costsand time. |
| PQC inhalation m - Preparation and quality control of modern dosage forms for alternative administration rout of biologics by inhalation (APVV-23-0508) | |
| Duration: | 1. 7. 2024 - 30. 6. 2028 |
| Evidence number: | APVV-23-0508 |
| Program: | APVV |
| Project leader: | PharmDr. Dráfi František, PhD., MPH |
| SAS cosolvers: | PharmDr. Bauerová Katarína, PhD., DrSc., PharmDr. Khademnematolahi Sasan , MVDr. Neradil Peter, Ing. Pádej Ivan, PharmDr. Poništ Silvester, PhD., Mgr. Pružinská-Koch Katarína, PhD, Ing. Švík Karol, CSc. |
| Annotation: | The use of biopharmaceuticals has drastically expanded with the development of recombinant DNA technology. The typical delivery rout of the innovative drugs is based on intra venous, sub cutaneous, or intra muscular application. Pulmonary drug delivery offers rapid and sustained drug delivery, high efficacy, no first-pass metabolism, and achievement of both local and systemic effects. Development of such biologic demands making particles/droplets that are sufficiently small, and nebulization of the solution to be inhaled. Both aspects affect product quality through decreased activity or protein aggregation. It is essential to optimize the drug formulation with the intended delivery system used. The aim of the project is development of reliable and functional formulations of mAbs and peptides for their inhalation application. We expect that our project will bring comprehensive standard operation protocols or guidelines for formulation of such biologics. |
| The influence of semantic representation and executive control on the structure and dynamics of idea generation | |
| Duration: | 1. 7. 2024 - 30. 6. 2028 |
| Evidence number: | |
| Program: | APVV |
| Project leader: | Mgr. Marko Martin, PhD. |
| SAS cosolvers: | Ing. Bendžala Štefan, RNDr. Bzdúšková Diana, PhD., RNDr. Cimrová Barbora, PhD., RNDr. Kimijanová Jana, PhD., Mgr. Kubinec Adam, Mgr. Michalko Drahomír, PhD., Mgr. Mitka Milan, PhD., MUDr. Riečanský Igor, PhD., Mgr. Rovný Rastislav, PhD., Mgr. Zelenayová Veronika |
| Annotation: | Human thinking emerges from a complex interaction of several neurocognitive processes and mechanisms that are yet poorly understood. Following the recent advances in cognitive psychology and neuroscience, in the present project, we introduce an integrative framework where the unfolding “stream of thought” is conceptualized as a dynamic memory process operating upon structured conceptual representations constrained by situational demands (i.e., contexts or goals). To understand how semantic cognition aids adaptive ideation, we will first develop an original memory paradigm, allowing us to deconstruct the complexity of thinking into fundamental and measurable processes and functions. Using these measures in a series of behavioral and psychophysiological experiments implementing a systematic manipulation of cognitive interference and load, we will further investigate the core determinants and predictors of ideational fluency at various levels of analysis. Moreover, we will employ unifocal as well as bifocal non-invasive electrical brain stimulation and rigorous experimentation to evaluate the causal involvement of the prefrontal cortex and the cerebellum in semantic memory retrieval and control, hence shedding light on the mechanisms and circuits supporting both spontaneous and controlled (i.e., goal-oriented) idea generation. Together, the proposed framework and paradigms bear strong potential to bring novel insights into the architecture of human thinking and inspire future diagnostic procedures or non-pharmacological treatments for individuals with neuropsychiatric conditions that manifest in aberrant memory functioning, language, or thinking. |
| Experimental real-life risk simulation approach: The effect of long-term exposure to a chemical mixture of pesticides, contaminants and food additives at low doses in extended one-generation reproductive toxicity study | |
| Duration: | 1. 1. 2024 - 31. 12. 2027 |
| Evidence number: | 2/0163/24 |
| Program: | VEGA |
| Project leader: | RNDr. Mach Mojmír, PhD. |
| SAS cosolvers: | Mgr. Bögi Eszter, PhD., Mgr. Bukatová Stanislava, PhD. , RNDr. Dubovický Michal, CSc. , MVDr. Neradil Peter, MVDr. Pecinová Romana, PhD., Doc. RNDr. Ujházy Eduard, CSc., Mgr. Zvozilová Alexandra |
| Other cosolvers: | Kršk |
| Annotation: | In real life, mixtures of xenobiotics can lead to a \'cocktail\' effect. Studies have shown that these mixtures can leadnot only to predictable additive effects but also to unpredictable synergistic, or antagonistic effects. From earlyintrauterine life till elderly, the individual is continuously exposed to chemicals with beneficial or detrimentaleffects depending on the doses, windows of exposure and combinations. Many of these exposures areconsidered risk factors for many diseases. These observations indicate the necessity of using improvedhazard-evaluation models, such as the real-life risk simulation (RLRS) scenario. The present project aims to toprovide an evaluation of the pre- and postnatal effects of mixture of chemicals (below NOAEL levels) ondevelopment as well as a thorough evaluation of systemic toxicity in pregnant and lactating females and youngand adult offspring. |
| Cardioprotective effects of mesenchymal stem cells and HMGB1 inhibitor after experimentally induced myocardial infarction | |
| Duration: | 1. 1. 2024 - 31. 12. 2027 |
| Evidence number: | 2/0131/24 |
| Program: | VEGA |
| Project leader: | RNDr. Cebová Martina, PhD. |
| SAS cosolvers: | MVDr. Barta Andrej, PhD., Mgr. Berényiová Andrea, PhD., Mgr. Bujnová Katarína, RNDr. Klimentová Jana, PhD., MUDr. Lakota Ján, CSc., doc. RNDr. Pecháňová Oľga, DrSc. |
| Annotation: | Myocardial infarction is a cardiovascular disease associated with remodeling as a result of ischemia. The absence of oxygen and nutrients during ischemia results in inflammation, oxidative damage, and tissue degeneration. For understanding of the onset and progression of myocardial protection mechanisms during ischemia, it is necessary to monitor signaling molecules that can block or reverse the pathological process. Despite advances in treatment, myocardial infarction still remains the leading cause of death in the world. The aim of the proposed project will be to clarify the initial molecular and morphological changes caused by both stem cell application and glycyrrhizin, an HMGB1 inhibitor, administrated after myocardial infarction with a focus on suppressing pro-inflammatory and pro-fibrotic pathways. The new results may provide information for targeted therapy aimed either at stem cells application or at the application of an HMGB1 inhibitor as an alternative for the myocardial infarction treatment. |
| Novel antidiabetic/antiobesty drugs as innovative pharmacotherapeutic tools for cardioprotection in experimental model of type 2 diabetes | |
| Duration: | 1. 1. 2024 - 31. 12. 2027 |
| Evidence number: | VEGA 2/0159/24 |
| Program: | VEGA |
| Project leader: | doc. RNDr. Barteková Monika, PhD. |
| SAS cosolvers: | Mgr. Duľová Ulrika, Mgr. Ferenczyová Kristína, PhD., Mgr. Kindernay Lucia, PhD., Mgr. Strapec Jakub |
| Annotation: | Ischemic heart disease and myocardial infarction represent major diseases associated with myocardial ischemia-reperfusion (I/R) injury. Although several effective pharmacological and non-pharmacological protective interventions against myocardial I/R have been identified, translation of knowledge into clinical practice is uncertain, also due to comorbidities suffered by cardiac I/R patients, including diabetes and obesity. On the other hand, recently described cardioprotective effects of known antidiabetic drugs give hope for a comprehensive solution for therapy of cardiovascular and metabolic diseases in one. The aim of the project will be to investigate the possibilities of cardioprotection against I/R injury using new drugs with antidiabetic and antiobesity effects in an experimental model of type 2 diabetes. Results of the project will contribute to expanding the possibilities of therapy for cardiometabolic diseases, and thus to better management of patients suffering from civilization diseases |
| Senogenic effects of environmental stressors in human skin cells and possibilities of senotherapy using natural and synthetic substances | |
| Duration: | 1. 1. 2024 - 31. 12. 2027 |
| Evidence number: | VEGA 2/0060/24 |
| Program: | VEGA |
| Project leader: | Ing. Račková Lucia, PhD. |
| SAS cosolvers: | Mgr. Kodríková Rebeka, Ing. Nemčovič Marek, PhD. |
| Annotation: | Current knowledge indicates that organism-environment interaction affects rate of aging of the organism.Oxidative stress and inflammation are among the main gerontogenic mechanisms triggered by environmentalstressors. These mechanisms are also linked to cellular senescence, process believed to contribute critically toaging.The skin, which is barrier organ of body, is constitutively exposed to various stimuli affecting itsmorphology and function.Therefore, skin exposome research can be considered paradigmatic,and itsimplementation can contribute to better understanding of aging in other organs as well.The aim of project is investigation of senogenic effects of various environmental stressors (such asoxidants,pollutants,UV radiation) also using new aging biomarkers. The scope of research also includestherapeutic efficacy of selected plant metabolites and synthetic compounds.The project will provide insight intogerontogenic and senotherapeutic mechanisms of substances studied in cellular skin models. |
| Investigating the involvement of connexin-43 in rat brown and white adipose tissue in mechanisms of cardiovascular risk and cardioprotection. | |
| Duration: | 1. 1. 2024 - 31. 12. 2027 |
| Evidence number: | VEGA 2/0133/24 |
| Program: | VEGA |
| Project leader: | RNDr. Egan Beňová Tamara, PhD. |
| Therapeutic intervention with bioactive compounds from bee products in experimental arthritis: evaluation of both articular and extra-articular complications | |
| Duration: | 1. 1. 2024 - 31. 12. 2027 |
| Evidence number: | 2/0079/24 |
| Program: | VEGA |
| Project leader: | PharmDr. Bauerová Katarína, PhD., DrSc. |
| SAS cosolvers: | Ahmad Waqar, PharmDr. Bauerová Katarína, PhD., DrSc., RNDr. Bučková Mária, PhD., PharmDr. Dráfi František, PhD., MPH, RNDr. Juránek Ivo, PhD., DrSc., PharmDr. Khademnematolahi Sasan , Ing. Majtán Juraj, DrSc., MBA, FIFST, PharmDr. Poništ Silvester, PhD., Mgr. Pružinská-Koch Katarína, PhD, Ing. Švík Karol, CSc. |
| Other cosolvers: | Lekárska fakulta UK v Bratislave |
| Annotation: | Bee products are a frequently studied due to their pharmacological properties. However, the identification ofsubstances responsible for their properties is absent. The aimof the project is to characterize the effect ofselected peptides and polyphenolic extracts from bee products on the articular manifestations of rheumatoidarthritis, but also on extra-articular manifestations with the aim of optimizing the conventional treatment. Adjuvant arthritis in rats will be used in the project. Polyphenolic extracts of bee pollen and honey will be tested, as well asmelittin from bee venom, 10-hydroxydecanoic acid from royal jelly and the bee peptide apisimin. In addition to biometric indicators, markers of inflammation and oxidative stress will be determined in plasma and in relevanttissues. Study of cardioprotective mechanisms and of mitochondrial energetics will be carried out. Finally, theeffectiveness of the most effective substance in combination with methotrexate and upadacitinib will be verified. |
| Therapeutic potential of natural antioxidants 7,8-dihydroxyflavone and Naringin in animal model of depression | |
| Duration: | 1. 1. 2024 - 31. 12. 2027 |
| Evidence number: | 2/0122/24 |
| Program: | VEGA |
| Project leader: | RNDr. Vranková Stanislava, PhD. |
| SAS cosolvers: | MVDr. Barta Andrej, PhD., Ing. Bendžala Štefan, RNDr. Klimentová Jana, PhD., MVDr. Ondičová Katarína, PhD., MUDr. Riečanský Igor, PhD., Mgr. Rovný Rastislav, PhD. |
| Annotation: | Depression is the most common mental disorder in the world. Pathomechanisms involved in the development of depression are mainly associated with the BDNF/TrkB/CREB signaling pathway. Affecting the BDNF/TrkB/CREBsignaling pathway is a critical therapeutic target for inducing adult hippocampal neurogenesis and antidepressanttherapy. Compounds capable of inducing rapid structuraland functional rearrangement of neuronal networks are particularly attractive. Several of these psychoplastogensare naturally occurring antioxidants, such as 7,8-dihydroxyflavone (7,8-DHF) and Naringin. The aim of our study is to investigate the effects of 7,8-DHF and Naringin, as well as their combinations, on the development of depressive-like symptoms in animal model of depression. Results of this project will contribute to elucidating thepathogenesis of depression and their treatment possibilities. |
| The effect sex and reproductive stage of females on the vasoregulatory role of sulfide and nitroso signaling pathways in metabolic syndrome | |
| Duration: | 1. 1. 2024 - 31. 12. 2027 |
| Evidence number: | 2/0153/24 |
| Program: | VEGA |
| Project leader: | Mgr. Berényiová Andrea, PhD. |
| Annotation: | Our studies demonstrated a key vasoregulatory role of nitric oxide (NO) and hydrogen sulfide (H2S) signaling invarious animal models of cardiovascular complications. In metabolic syndrome (MS) induced by changed diet, wereported that the interaction of these signaling pathways is disrupted, and H2S donor application can alleviate thepathological manifestations of MS. Moreover, in hypertriglyceridemic rats (HTG) we observed an endothelialdysfunction that was not only associated with reduced NO-synthase activity but also with endogenously producedH2S. Previous studies have focused on cardiovascular changes mainly in males, while studies on HTG femalesare missing. The project will examine the influence of gender and reproductive status of females HTG rats withthe aim of revealing possible differences in vasoactive regulatory mechanisms. At the same time, it willinvestigate the possible beneficial effects of flavonoid administration on cardiovascular complication associatedwith postmenopausal MS. |
| The role of sex hormones in the a1AMPK- mediated vascular protection during the development of the metabolic syndrome | |
| Duration: | 1. 1. 2024 - 31. 12. 2027 |
| Evidence number: | 2/0123/24 |
| Program: | VEGA |
| Project leader: | Ing. Kvandová Miroslava, PhD. |
| SAS cosolvers: | RNDr. Vlkovičová Jana, PhD., Mgr. Zemančíková Anna, PhD. |
| Annotation: | Disruption of vascular homeostasis caused by reduced nitric oxide bioavailability due to oxidative stress and inflammation is the most severe complication of metabolic syndrome (MetS). Therefore, it is essential to identify the key factors that protect the endothelium and improve the primary and secondary prevention of cardiovascular diseases. Such a factor may be a1AMP-dependent protein kinase (a1AMPK), as it may be involved in improving metabolic control. The project focuses on risk factors affecting endothelial function during MetS and a1AMPK as a potential tool to modify these factors in the context of gender differences, as sex hormones can regulate a1AMPK. The project’s originality is based on a comprehensive assessment of changes in endothelial function during MetS with a clear focus on vascular endothelium and gender differences. The results of this study represent a potential tool to increase the quality of life and reduce the economic burden associated with treating this cardiometabolic disease. |
| Research of plants with therapeutic potential in surgery, dermatology, and dentistry: phytochemical analysis, biological effects, and study of mutual interactions of their constituents. | |
| Duration: | 1. 1. 2024 - 31. 12. 2027 |
| Evidence number: | VEGA 1/0170/24 |
| Program: | VEGA |
| Project leader: | Ing. Račková Lucia, PhD. |
| The role of in Wnt signaling in processes associated with effects of doxorubicin. | |
| Duration: | 1. 1. 2024 - 31. 12. 2027 |
| Evidence number: | VEGA 2/0169/24 |
| Program: | VEGA |
| Project leader: | RNDr. Barančík Miroslav, DrSc. |
| BIOCARD - - | |
| Duration: | 1. 7. 2023 - 30. 6. 2027 |
| Evidence number: | APVV-22-0264 |
| Program: | APVV |
| Project leader: | Ing. Ferko Miroslav, PhD. |
| Annotation: | Oxygen-limited supply significantly increases the myocardial energy requirements. The onset of compensatorymechanisms against this disorder is associated with regulation at the level of cardiac mitochondria. It ismitochondrial dysfunction that is currently the goal of a therapeutic cardioprotective strategy. This project willcombine the latest scientific insights with state-of-the-art methodological approaches. A key aspect of thepresented research is to ensure sufficient energy production in the heart in conditions of increased energyrequirements caused by reduced oxygen utilization and ischemic heart disease in combination with various types ofpreconditioning. The use of modern methodology will allow for investigation into the complex structure ofmitochondrial protein signaling pathways, their regulations, proteome and metabolome alterations in heart andmitochondria. Description and comprehension of complex system of protein interactions can help identify signalingpathways in cardioprotection processes. Changes at the level of mitochondrial respiratory chain complexes that play an important role in the cellular energy maintenance will also be identified. One of the considered mechanismsof cardioprotection is the inhibition of mitochondrial permeability transition pores (mPTP) opening. Regulation ofmPTP in terms of changes of individual proteins has already been presented. We aim to contribute to theunderstanding of the protein interactions presumably related to the protective modulation of mPTP. In connectionwith the remodeling of mitochondrial function, calcium homeostasis and signaling of free oxygen radicals will alsobe monitored. The presented project will deal with the stimulation of adaptation processes in order to contribute tothe elimination of mitochondrial dysfunction and ensure the maintenance of dynamic balance under conditions ofenergy deprivation in diseased heart. |
| ITAGES - Identification of stress-induced alterations in expression of NRF2 target genes in rat models of prehypertension: the effect of comorbid hypertriglyceridemia and dimethyl fumarate treatment | |
| Duration: | 1. 7. 2023 - 30. 6. 2027 |
| Evidence number: | APVV-22-0296 |
| Program: | APVV |
| Project leader: | RNDr. Bernátová Iveta, DrSc. |
| SAS cosolvers: | MSc. Anjum Anjum, RNDr. Bališ Peter, PhD., MVDr. Barta Andrej, PhD., MSc. Bozkurt Aybuke, RNDr. Cigáň Alexander, CSc., Ing. Dvurečenskij Andrej, PhD., Mgr. Kaločayová Barbora, PhD., Mgr. Kluknavský Michal, PhD., Ing. Kvandová Miroslava, RNDr. Líšková Silvia, PhD., Mgr. Magyarová Silvia, Ing. Majerová Melinda, PhD., Ing. Maňka Ján, CSc., Mgr. Mičurová Andrea, PhD., Mgr. Škrátek Martin, PhD. |
| Annotation: | The nuclear transcription factor erythroid 2-related factor 2 (NRF2) is a key molecular link between several noncommunicable diseases, as it regulates the expression of approximately 250 target genes, including those involved in maintenance of redox balance, the development of metabolic disorders, cardiovascular and liver diseases, as well as in immune responses. Borderline elevated blood pressure (prehypertension) is a common cardiovascular disorder in humans, and elevated blood pressure has been found to be positively correlated with triglyceride levels. In addition, chronic stress is an etiological factor in the development of non-communicable diseases, including elevated blood pressure and hypertriglyceridemia (HTG). In experimental studies, borderline hypertensive rats (BHR) and hypertriglyceridemic rats (HTGR) are suitable models of prehypertension without and with comorbid hypertriglyceridemia. These models are relevant for investigating the effects of stress as well as for investigating the role of changes in expression of NRF2 target genes in the development of hypertension associated with metabolic diseases. To understand better the role of NFR2 as well as the impact of chronic social stress on thementioned diseased states, the aims of this project are: 1) to identify differences in expression of NRF2 target genes in two experimental models of prehypertension - without (in BHR) and with (in HTGR) comorbid HTG - in control conditions and during chronic social stress, 2) to determine if NRF2 activator dimethyl fumarate can reduce stress-induced pathologies in prehypertensive rats, especially in those with comorbid HTG, and 3) to specify a set of suitable whole blood RNA biomarkers for evaluation of changes in NRF2 target genes in prehypertension and HTG and those genes altered by chronic social stress. |
| CARDIOEND - Cardiovascular protection mediated by alpha 1 AMPK against metabolic syndrome-mediated endothelial dysfunction - identifying new risk factors | |
| Duration: | 1. 7. 2023 - 30. 6. 2027 |
| Evidence number: | APVV-22-0154 |
| Program: | APVV |
| Project leader: | Ing. Kvandová Miroslava, PhD. |
| SAS cosolvers: | RNDr. Bališ Peter, PhD., doc. RNDr. Barteková Monika, PhD., RNDr. Bernátová Iveta, DrSc., Mgr. Csicsátková Nikoleta, PhD., Mgr. Duľová Ulrika, Mgr. Ferenczyová Kristína, PhD., Mgr. Grman Marián, PhD., RNDr. Hlaváčová Nataša, PhD., prof. PharmDr. Ježová Daniela, DrSc., RNDr. Karailiev Peter, PhD., Mgr. Kluknavský Michal, PhD., Mgr. Magyarová Silvia, doc. RNDr. Pecháňová Oľga, DrSc., doc. MUDr. Radošinská Jana, PhD., Mgr. Strapec Jakub, Mgr. Suroviaková Katarína, doc. MUDr. Török Jozef, CSc., Mgr. Zemančíková Anna, PhD. |
| Annotation: | Disruption of vascular homeostasis caused by decreased nitric oxide bioavailability oxide due to oxidative stress and inflammation is the most serious complication of metabolic syndrome (MetS), leading to increased morbidity and mortality. There is an unmet need to identify key factors that prevent or protect vascular endothelium and thus improve primary and secondary prevention of cardiovascular diseases. It appears that AMP-dependent protein kinase (AMPK) may be such a factor. Its protective properties and positive effect on endothelial function and oxidative stress are already known. These unique properties suggest that AMPK may be involved in improving metabolic control during MetS, but still, the molecular changes due to α1AMPK-related dysregulation during MetS development are poorly understood. The project focuses on risk factors affecting endothelial function during MetS and the AMPK as a potential tool to modify those risk factors resulting in MetS prevention or treatment. The originality of the project is based on a comprehensive evaluation of functional, molecular, and biochemical changes in endothelial function, inflammation, and metabolic senescence during MetS with a detailed focus on vascular endothelium - proliferation, senescence, and apoptosis. The focus will be put on risk factors affecting endothelial function such as the interaction/adhesion of leukocytes with the vascular endothelium and the AMPK-dependent role of erythrocytes during MetS development. The project will be enriched by the study of phenotypic and molecular changes at the level of the CNS, with an emphasis on neuroinflammation and behavioral changes. Importantly, the project has a translation character, as human studies in patients with MetS will also be performed. The obtained results may represent a potential tool for improving the current population’s health and reducing the economic burden associated with the treatment of this cardiometabolic disease. |
| CardCa2+CNS - Molecular mechanisms implicated in corticosteroid-monoamine interaction in stress-related cardio- and neuropathologies | |
| Duration: | 1. 7. 2023 - 30. 6. 2027 |
| Evidence number: | APVV-22-0061 |
| Program: | APVV |
| Project leader: | RNDr. Mach Mojmír, PhD. |
| SAS cosolvers: | Mgr. Bukatová Stanislava, PhD. , RNDr. Májeková Magdaléna, PhD., Mgr. Zvozilová Alexandra |
| Annotation: | Stress is defined as an organism’s response to various stressors jeopardizing the homeostasis. Stressors accompany living organisms all through their life, when the first exposure happens even before the birth (e.g., maternal infection during the gestation). Stress is not necessarily harmful; controlled exposure to the certain stressors might be even beneficial (e.g., cognitive behavioral therapy). On the other side, stress can also be involved in certain heart and brain disorders, which are the worldwide leading causes for disability and mortality. Based on our previous results in rats, we hypothesize that interaction between corticosteroids and monoamines is a factor determining whether certain stressor, administered to the organism of the specific sex, will be harmful, neutral, or even beneficial. We aim to perform a further investigation of corticosteroid-monoamine interaction in rat model of prenatal stress (maternal infection during the gestation caused by LPS administration) and to assess a role of Ca2+ signaling, which decodes diverse extracellular signals into specific cellular responses. Particularly, we will focus on investigation of changes caused by prenatal stress at the level of cardiomyocyte contractility and excitability of serotonin and dopamine neurons in the midbrain. Ca2+ signaling as a potential intracellular effector of corticosteroid-monoamine interaction will be monitored at the level of intracellular Ca2+ channels, which are considered as the main components of Ca2+ signaling in cardiomyocytes as well in neurons. We will also test pyridoindoles as the novel treatment strategies for the stress-related cardiovascular and neurological disorders. This will include in silico modeling (computer simulations of drug interactions) and in vivo treatment. |
| On the trace of mitochondrial chloride channel identity. | |
| Duration: | 1. 7. 2023 - 30. 6. 2027 |
| Evidence number: | APVV-22-0085 |
| Program: | APVV |
| Project leader: | Ing. Ferko Miroslav, PhD. |
| Annotation: | Mitochondrial chloride channels are involved in the regulation of the mitochondrial membrane potential deltaΨm. Inin vitro conditions, it was observed that oxidative stress results in oscillations of deltaΨm, which leads to theshortening of the action potential on the plasma membrane of cardiomyocytes and to the occurrence ofarrhythmias, mediated by the production of ATP in the mitochondria. At the level of the whole heart, arrhythmiaswere observed as a consequence of ischemia-reperfusion. Specific ligands of the translocator protein (TSPO)prevent the occurrence of post-ischemic arrhythmias. The use of a non-specific chloride channel blocker led to thesame effect. TSPO ligands inhibit the mitochondrial chloride channels at nanomolar concentrations, suggesting thatthe TSPO protein mediates the chloride channel block. Thus, TSPO is likely to be in close contact with the chloridechannel. Mitochondrial chloride channels are well described at the electrophysiological level, but their molecularidentity remains unclear. Recently, two isoforms of chloride intracellular channel family (CLICs) have been shownto be localized in mitochondria. However, CLIC channels have only been described in an artificial system -overexpressed in host cells. Mitochondrial chloride channels from native membranes are assumed to be identicalto one of the two mitochondrial CLIC isoforms. The aim of the presented project is to verify the hypothesis that themeasured native chloride channels from cardiac mitochondria are members of the CLIC family and whether the given CLIC isoform and TSPO are in close physical contact. We assume that the obtained results will help to clarify the molecular identity of the mitochondrial chloride channel, which represents a significant potential target forpreventing the occurrence of post-ischemic arrhythmias. |
| HYDMIM - Effects of mesenchymal stem cells and HMGB1 inhibitor on cardiovascular system after experimentally induced myocardial infarction in hypertension and diabetes mellitus | |
| Duration: | 1. 7. 2023 - 30. 6. 2027 |
| Evidence number: | APVV-22-0271 |
| Program: | APVV |
| Project leader: | RNDr. Cebová Martina, PhD. |
| SAS cosolvers: | MVDr. Barta Andrej, PhD., Ing. Bendžala Štefan, Mgr. Bujnová Katarína, Bc. Hikl Jakub, RNDr. Klimentová Jana, PhD., MUDr. Lakota Ján, CSc., RNDr. Vranková Stanislava, PhD. |
| Other cosolvers: | Vojtková Mária doc. Ing. PhD. |
| Annotation: | Myocardial infarction is a serious disease of the coronary arteries, when part of the heart muscle dies and cardiac remodeling occurs as a result of persistent ischemia. The lack of oxygen and nutrients during ischemia results in inflammation, oxidative damage, and tissue degeneration. For a comprehensive understanding of the onset and progression of myocardial protection mechanisms during ischemia, it is necessary to monitor protective signaling molecules that can block or reverse the pathological process. Despite significant progress in the treatment of diseases of the cardiovascular system, myocardial infarction still remains the main cause of death in the world, especially in elderly patients with associated diseases such as hypertension and diabetes mellitus. The aim of the proposed project will be to clarify the significance of the nitric oxide signaling pathway after myocardial infarction in conditions of selected comorbidities. We will define the initial molecular and morphological changes that are caused by either the application of stem cells or glycyrrhizin, an HMGB1 inhibitor, applied after myocardial infarction. We will also examine the effectiveness of stem cells and glycyrrhizin to suppress pro-inflammatory and pro-fibrotic pathways with focus on PI3K-Akt-eNOS signaling pathway and JNK / Bax and TLR4 / NF-κB signaling pathway. The new results may provide information for targeted therapy aimed at the application of stem cells after myocardial infarction. In addition, in patients who are not suitable candidates for the given treatment, the application of an HMGB1 inhibitor can be an alternative for the treatment of myocardial infarction. |
| Targeted suppression of pro-inflammatory and pro-fibrotic signalling pathways to prevent life-threatening heart failure and malignant arrhythmias | |
| Duration: | 1. 1. 2023 - 31. 12. 2026 |
| Evidence number: | |
| Program: | VEGA |
| Project leader: | RNDr. Szeiffová Bačová Barbara, PhD. |
| EXPERIMENTAL STUDY OF THE EFFECTS OF MATERNAL DEPRESSION AND ANTIDEPRESSANTS CITALOPRAM AND SERTRALINE ON POSTNATAL DEVELOPMENT OF RAT OFFSPRING | |
| Duration: | 1. 1. 2023 - 31. 12. 2026 |
| Evidence number: | 2/0133/23 |
| Program: | VEGA |
| Project leader: | RNDr. Dubovický Michal, CSc. |
| SAS cosolvers: | Mgr. Bögi Eszter, PhD., Mgr. Bukatová Stanislava, PhD. , RNDr. Mach Mojmír, PhD., MVDr. Pecinová Romana, PhD., Doc. RNDr. Ujházy Eduard, CSc. |
| Annotation: | Depressive disorders affect around 20% of women during pregnancy and breastfeeding. The most frequently prescribed antidepressants during pregnancy are selective serotonin reuptake inhibitors (SSRIs). However, the safety of their use in the treatment of maternal depression is controversial. The US Food and Drug Administration (FDA) classifies these antidepressants as Category C drugs, which means that there are currently no sufficient well-controlled studies to assess the risk of their administration to pregnant and breastfeeding women. In our experimental project, we will focus on researching citalopram and sertraline and their possible adverse (or therapeutic) effects on rat brain development when administered to pregnant rats alone or in combination with induced maternal depression. With this research, we want to contribute to a more comprehensive characterization of both drugs in terms of their safety in the treatment of maternal depression. |
| N/A - Pharmacological intervention in the treatment of cachexia by administering natural extracts (Crocus sativus and Ginkgo biloba) and substances (melittin, saffron, crocin, kaempferol and isorhamnetin) in combination with methotrexate and dexamethasone in an | |
| Duration: | 1. 1. 2023 - 31. 12. 2026 |
| Evidence number: | VEGA 2/0126/23 |
| Program: | VEGA |
| Project leader: | PharmDr. Poništ Silvester, PhD. |
| SAS cosolvers: | PharmDr. Bauerová Katarína, PhD., DrSc., PharmDr. Dráfi František, PhD., MPH, Ing. Mihalová Danica, PharmDr. Taghdisiesfejír Mohsen |
| Other cosolvers: | Tóth Jaroslav, Mgr., PhD., |
| Annotation: | Rheumatoid arthritis (RA) is a chronic inflammatory disease that affects the synovial joints and is also associated with extra-articular manifestations, including cachexia. Standard treatment of RA with methotrexate (MTX) and glucocorticoids (GC) may worsen cachexia. Thus, an important strategy of this project will be the suppression of cachexia using combination therapy, which will be based on the addition of natural anti-inflammatory substances to MTX and GC. In experimental arthritis, we will also investigate the effect of drugs and natural substances on markers of catabolism (myostatin and E3 ubiquitin-protein ligase) and anabolism (IGF-1, ghrelin, and testosterone) of skeletal muscle, on markers of systemic inflammation (IL-1beta, TNF-alpha, IL-6, MCP-1, IL-17A, MMP-9) and oxidative stress (4-hydroxynonenal, protein carbonyls, glutathione peroxidase, catalase) in plasma, which will help us to elucidate the mechanisms of inflammatory cachexia and it’s affecting by monotherapy and combination therapy. |
| In vitro study of antioxidative/antiinflammatory effects of natural and synthetic compounds. In vivo assessment of medicinal effects of selected compounds in experiments of healing skin wounds. | |
| Duration: | 1. 1. 2023 - 31. 12. 2026 |
| Evidence number: | 2/0008/23 |
| Program: | VEGA |
| Project leader: | RNDr. Valachová Katarína , PhD. |
| SAS cosolvers: | RNDr. Juránek Ivo, PhD., DrSc., Dr.rer.nat., Ing. Kanďárová Helena, ERT, Ing. Pádej Ivan, Ing. Šoltés Ladislav, DrSc., Ing. Švík Karol, CSc. |
| - | |
| Duration: | 1. 1. 2023 - 31. 12. 2026 |
| Evidence number: | 2/0025/23 |
| Program: | VEGA |
| Project leader: | doc. RNDr. Pecháňová Oľga, DrSc. |
| Neurocognitive mechanisms of semantic representation and control | |
| Duration: | 1. 1. 2023 - 31. 12. 2026 |
| Evidence number: | 2/0052/23 |
| Program: | VEGA |
| Project leader: | Mgr. Marko Martin, PhD. |
| SAS cosolvers: | Mgr. Bajzová Barbora, Ing. Bendžala Štefan, RNDr. Cimrová Barbora, PhD., Mgr. Kubinec Adam, Mgr. Marko Martin, PhD., Mgr. Michalko Drahomír, PhD., Mgr. Mitka Milan, PhD., MUDr. Riečanský Igor, PhD., Mgr. Rovný Rastislav |
| Annotation: | Semantic cognition underpins the processing, organization, and fluid retrieval of knowledge (facts, concepts, and their relations) stored in memory. It regulates mental processes and adaptive behavior, whereas deterioration of this system is present among several neuropsychiatric disorders and diseases. The aim of this project is to identify cognitive and neurobiological mechanisms that support the ability to search and retrieve conceptual representations within semantic memory. For this purpose, we will carry out a set of original experiments that combine systematic manipulation of cognitive interference, the measurement of cognitive load (effort) using pupillometry, and non-invasive (transcranial) electrical brain stimulation. Via such interdisciplinary approach, we intent to characterize key neurocognitive determinants of automatic and control (executive) functions of the human semantic system, which may inspire effective interventions for their enhancement. |
| Neuroprotective and cardioprotective potential of phenol acids in the prevention of civilization diseases | |
| Duration: | 1. 1. 2023 - 31. 12. 2026 |
| Evidence number: | VEGA 2/0018/23 |
| Program: | VEGA |
| Project leader: | RNDr. Gáspárová Zdenka, PhD. |
| SAS cosolvers: | MVDr. Bezek Štefan, DrSc., RNDr. Dubovický Michal, CSc. , RNDr. Juránek Ivo, PhD., DrSc., RNDr. Knezl Vladimír, PhD., Ing. Lepáček Marek, Ing. Pádej Ivan, Ing. Švík Karol, CSc. |
| Annotation: | The risk of the civilization disease can be reduced by adjusting the lifestyle and a diet low in fat and increasing the intake of vegetables and fruits rich in flavonoids. These include phenolic acids (PA), small molecules with good bioavailability, and beneficial effects on the body. The project is focused on the cardioprotective and neuroprotective effects of PA on the heart and hippocampus of rats in vitro. After selecting the most effective PA from in vitro experiments, this will be tested in vivo in a model of a metabolic syndrome induced by a high fat-fructose diet. A project innovation lies in (i) the use of promising low molecular weight PA, and (ii) the application of magnetic resonance spectroscopy for non-invasive monitoring of the neurochemical profile changes in the rat brain. The determination of inflammation and oxidative stress markers offers to characterize the mechanism of action of the selected PA. The behavioral test (NOR) will provide data on learning and memory improvements. |
| 2/0091/23 - The contribution of new nano-carrier drug delivery systems to the enhancement of the anti-inflammatory effect of D-limonene, phellandrene, isoborneol and chrysophanol studied in vivo (2/0091/23) | |
| Duration: | 1. 1. 2023 - 31. 12. 2026 |
| Evidence number: | 2/0091/23 |
| Program: | VEGA |
| Project leader: | PharmDr. Dráfi František, PhD., MPH |
| SAS cosolvers: | PharmDr. Bauerová Katarína, PhD., DrSc., Mgr. Chrastina Martin, PharmDr. Khademnematolahi Sasan , Ing. Mihalová Danica, PharmDr. Poništ Silvester, PhD., PharmDr. Taghdisiesfejír Mohsen, Mgr. Tóthová Nikola |
| Other cosolvers: | Bilková Andrea, Špaglová Miroslava, Kiňová Sepová Hana, Mikušová Veronika, Žigrayová Dominika (doktorand), Ferková Jarmila (doktorand). |
| Annotation: | Based on the scientific literature we hypothesize that an optimal anti-inflammatory effect of a selected naturalsubstance after its oral administration in its new nano-carrier drug delivery systems (NCDDS) might beneficiallymodulate immune processes in inflammatory diseases as in rheumatoid arthritis (RA). Adjuvant arthritis (AA) is used as one of the in vivo RA models to evaluate the pharmacology of molecules tested. High bioavailability will be achieved by the technological adjustment of the molecules into NCDDS (nanoemulsions and liposomes). Along with other parameters evaluated and focused mainly on inflammation, we will analyze the ability to reduce bone erosion and/or synovitis by the RANKL/RANK/osteoprotegerin signalling pathway. The significant benefit will be statistically assessed by their dose-dependency evaluation and possible synergic/additive pharmacological determination of concomitantly applied standards as methotrexate and upadacitinib, administered both in (sub)therapeutic doses. |
| - | |
| Duration: | 1. 1. 2023 - 31. 12. 2026 |
| Evidence number: | 1/0048/23 |
| Program: | VEGA |
| Project leader: | doc. RNDr. Pecháňová Oľga, DrSc. |
| Cardiac mitochondrial bioenergetics regulated by reduced oxygen consumption: In-depth proteomic analysis of cardioprotective signaling pathways. | |
| Duration: | 1. 1. 2023 - 31. 12. 2026 |
| Evidence number: | 2/0016/23 |
| Program: | VEGA |
| Project leader: | Ing. Ferko Miroslav, PhD. |
| Annotation: | Reduced oxygen utilization significantly increases the myocardial energy requirements. The compensatory mechanisms against this serious metabolic disorder is associated with regulation of cardiac mitochondria. It is mitochondrial dysfunction that is currently the goal of a therapeutic cardioprotective strategy, effective against energy and dynamic imbalance. Part of the identification of preconditioning-induced adaptation processes will be the monitoring of the role of mitochondria on redox equilibrium, signaling of free oxygen radicals, changes in oxidative phosphorylation and energy pathways, mitochondrial dynamics and ion homeostasis. The definition of hypoxic damage, the effect of preconditioning and the identification of a potential cardioprotective signal carrier will be indicated by proteomic and metabolomic analyzes by LC-MS. The comprehensive analysis will provide detailed information on changes of proteins as potential markers as well as the characteristics of their signaling pathways. |
| DiPrev - Dimethyl fumarate as a potential tool for the prevention of cardiovascular and hepatic disorders associated with Western diet in borderline hypertensive rats | |
| Duration: | 1. 9. 2024 - 31. 8. 2026 |
| Evidence number: | 09I03-03-V04-00427 |
| Program: | Plán obnovy EÚ |
| Project leader: | RNDr. Bernátová Iveta, DrSc. |
| SAS cosolvers: | Mgr. Kluknavský Michal, PhD. |
| SGLT2 Cardioprot - Cardioprotective effect of SGLT2 inhibition in heart failure: the role of RISK and SAFE pathway | |
| Duration: | 1. 9. 2024 - 31. 8. 2026 |
| Evidence number: | 09I03-03-V04-00389 |
| Program: | Plán obnovy EÚ |
| Project leader: | Mgr. Farkašová Veronika, PhD |
| Annotation: | Heart failure (HF) is the final stage in several cardiovascular diseases (CVD) (cardiomyopathies, valvular or ischemic heart disease, acute myocardial infarction and many others). Myocardial infarction (MI) remains the most common cause of HF worldwide. For almost 50 years HF has been recognised as a determinant of adverse prognosis after MI. Although the patients that successfully survive MI live longer, the alteration of the heart muscle will manifest later on by chronic failure of its pumping function. Potential reasons of that may be related to the complexity of mechanisms of HF and the requirement for multitarget effects of optimal cardioprotection. Sodium-glucose co-transporter 2 (SGLT-2) inhibitors are the newest class of antidiabetic drugs. Recently, clinical trials reported the cardiovascular benefits of empagliflozin, an SGLT-2 inhibitor, by significantly decreasing the incidence of hospitalization associated with HF and cardiovascular-cause death rate in diabetic patients with CVD and in HF patients. In addition, SGLT2 inhibitors (SGLT2i) exert cardioprotective effects in animal models of acute MI through a reduction of infarct size and a subsequent attenuation of HF development. Chronic treatment with Empagliflozin in mice with type 2 diabetes showed that the drug increased both the phosphorylation and the expression of cardiac signal transducer and activator of transcription 3 (STAT-3) at early reperfusion. STAT-3 is one of the main signaling molecules in the survivor-activating factor enhancement (SAFE) pathway. SAFE, together with the pro-survival reperfusion injury salvage kinase (RISK) pathway, are considered major mediators of cardioprotection against I/R injury, showing potential for SGLT2 inhibition as a cardioprotective drug candidate.The project aims to evaluate the effect of pharmacological conditioning with an SGLT2 inhibitor on cardiac resistance to acute myocardial infarction and subsequent HF and to determine the role of RISK and SAFE pathways in pharmacological conditioning with an SGLT2 inhibitor in hearts subjected to acute myocardial infarction and subsequent heart failure. |
| MITPROT - Heart mitochondria proteomic mapping: Uncovering potential signaling pathways | |
| Duration: | 1. 9. 2024 - 31. 8. 2026 |
| Evidence number: | 09I03-03-V04-00437 |
| Program: | Plán obnovy EÚ |
| Project leader: | Mgr. Andelová Natália, PhD. |
| Annotation: | Exposure of the organism to limited access to oxygen is a significant stimulus in inducing cardioprotection effective against mitochondrial dysfunction. From the point of view of possible initiators of endogenous myocardium protection, hypoxia appears as a potential trigger of adaptation processes. Hypoxia-induced stimulation of the adaptive response induced by preconditioning represents an effective tool for maintaining the bioenergetic balance of the myocardium exposed to ischemia/reperfusion injury. Due to the dynamic nature of mitochondria, research attention is increasingly focused on their proteomic changes. Proteins are proving to be promising prognostic and diagnostic biomarkers. Modern analytical methods, such as mass spectrometry, which allows complex mapping of proteins and their changes, have a promising potential. Applying biostatistical approaches offers new concepts for studying protein-protein interactions (PPI) and characterizing signaling pathways involved in mitochondrial cardioprotective processes. Identifying mitochondrial proteome changes, elucidating calcium and reactive oxygen species signaling, regulating mitochondrial permeability transition pore opening, and studying PPI could provide a breakthrough understanding of signaling pathways from mitochondria to overall myocardial physiology. |
| Edifu - The effect of dimethyl fumarate on nuclear factor erythroid 2-related factor 2 activation and redox balance in chronic stress-exposed female rats with mild hypertension and comorbid hypertriglyceridemia | |
| Duration: | 1. 9. 2024 - 31. 8. 2026 |
| Evidence number: | 09I03-03-V04-00477 |
| Program: | Plán obnovy EÚ |
| Project leader: | Mgr. Mičurová Andrea, PhD. |
| Annotation: | The number of hypertensive adults worldwide has dramatically increased in last 30 years. Hypertension found together with other comorbidities presents a risk factor for development of several diseases. Nowadays, stress is considered to be significant factor involved not only in development, but also progression of cardiovascular, psychological and other diseases. Several studies associated long-lasting stress with disturbances in redox balance in various tissues, mainly with increased reactive oxygen species production or decreased activity of antioxidant enzymes. Nuclear factor erythroid 2-related factor 2 (NRF2) is a transcription factor that regulates the cytoprotection against toxic and oxidative insults through the expression of genes involved in antioxidant defense. Interestingly, recent studies indicate that expression of NRF2 is decreased under chronic stress and leads to significant changes in redox homeostasis. Since hypertension and comorbid hypertriglyceridemia are often found together and many adults are exposed to chronic stressors, the aim of this project is to specify the chronic stress-induced behavioural changes, disturbances in redox balance, expression of NRF2 and its activation with dimethyl fumarate in various tissues of female experimental model of prehypertension with comorbid triglyceridemia. |
| SUFIBAR - Targeted suppression of pro-inflammatory and pro-fibrotic signaling pathways to prevent heart failure and occurrence of malignant arrhythmias | |
| Duration: | 1. 7. 2022 - 30. 6. 2026 |
| Evidence number: | APVV-21-0410 |
| Program: | APVV |
| Project leader: | RNDr. Szeiffová Bačová Barbara, PhD. |
| SAS cosolvers: | Mgr. Andelová Katarína, PhD., Mgr. Andelová Natália, PhD., RNDr. Barančík Miroslav, DrSc., RNDr. Egan Beňová Tamara, PhD., Mgr. Farkašová Veronika, PhD, Mgr. Ferenczyová Kristína, PhD., Ing. Ferko Miroslav, PhD., Mgr. Fogarassyová Mária, Mgr. Kaločayová Barbora, PhD., RNDr. Knezl Vladimír, PhD., RNDr. Kura Branislav, PhD., RNDr. Okruhlicová Ľudmila, CSc., D.h.c., Prof., MUDr. Slezák Ján, DrSc., FIACS, Mgr. Svetláková (Boťanská) Barbora, PhD., RNDr. Sýkora Matúš, PhD., RNDr. Tribulová Narcisa, DrSc., RNDr. Vlkovičová Jana, PhD. |
| Annotation: | Heart failure is characterized by a progressive reduction in cardiac output and occurrence of malignant arrhythmias resulting in substantial morbidity and mortality worldwide. Cardiac fibrosis, the key factor contributing to these life-threatening events, is still unresolved problem in clinic. Detection and management of myocardial fibrosis suffer from a lack of precision, therefore, novel approaches are extremely needed. We hypothesize that the determination of myocardial fibrosis phenotypes in a disease-specific way may reveal more precisely molecular targets for efficient prevention and/or treatment. The idea of the project is to differentiate myocardial fibrosis phenotypes via assessment of circulating markers of oxidative stress, inflammation and pro-fibrotic components along with determining the activation of actual signaling pathways and extent of fibrosis. In the same time to explore efficacy of selected compounds, AT1 receptor blocker, ACE inhibitor, melatonin, triiodothyronine, metoprolol, omega-3 fatty acids and molecular hydrogen, to suppress pro-inflammatory and pro-fibrotic signaling pathways including purinergic signaling mediated by connexin-43 hemichannels and panexin-1 channels and to prevent or attenuate adverse structural and electrical remodeling. Novel findings may provide fundamental input to targeted therapy aimed to reduce myocardial fibrosis burden and challenge to realize well designed clinical trials. |
| CARDIOPROT - New aspects of cardioprotection by natural antioxidants: role of ageing and lifestyle-related comorbidities | |
| Duration: | 1. 7. 2022 - 30. 6. 2026 |
| Evidence number: | APVV-21-0194 |
| Program: | APVV |
| Project leader: | doc. RNDr. Barteková Monika, PhD. |
| SAS cosolvers: | RNDr. Bališ Peter, PhD., RNDr. Barančík Miroslav, DrSc., Mgr. Berényiová Andrea, PhD., Mgr. Farkašová Veronika, PhD, Mgr. Ferenczyová Kristína, PhD., Mgr. Fogarassyová Mária, Mgr. Kaločayová Barbora, PhD., Mgr. Kindernay Lucia, PhD., RNDr. Kura Branislav, PhD., MUDr. RNDr. Púzserová Angelika, PhD., Mgr. Svetláková (Boťanská) Barbora, PhD., RNDr. Sýkora Matúš, PhD., RNDr. Szeiffová Bačová Barbara, PhD., Mgr. Šnúriková Denisa, RNDr. Vlkovičová Jana, PhD. |
| Other cosolvers: | Radoš |
| Annotation: | Despite the important progress in the treatment of cardiovascular disease (CVD), the new therapeutic strategies as well as mechanisms involved are still being extensively studied to reach the optimal efficiency of the therapy. Ischemia/reperfusion (I/R) injury represents a clinically relevant problem associated with CVD (including ischemic heart disease and myocardial infarction) as well as with cardiac surgery. Natural antioxidants including flavonoid quercetin and several catechins have been shown to exert protective effects against cardiac I/R injury. However, most of the experimental studies have been performed in young healthy animals what is not corresponding to the situation in real life where the patients prone to acute ischemic event (myocardial infarction) are usually aged people suffering from some comorbidities such as hypertension or metabolic disorders. Thus the aim of the current project is to reveal the real therapeutic potential of selected natural antioxidants, quercetin and epicatechin against cardiac I/R injury in aged subjects and subjects suffering from selected metabolic comorbidities (type 2 diabetes, hypertriglyceridemia) and hypertension. Another goal of the project is to uncover intra- as well as intercellular mechanisms involved in the action of selected antioxidantss in individuals with comorbidities exposed to cardiac I/R, including their interactions with mechanisms involved in development of selected comorbidities. Meeting the objectives of the project will significantly help to better management of patients suffering from CVD, particularly from acute myocardial infarction |
| Aldo-keto reductase inhibitors in the personalized therapy of several types of cancer | |
| Duration: | 1. 1. 2022 - 31. 12. 2025 |
| Evidence number: | 2/0087/22 |
| Program: | VEGA |
| Project leader: | Ing. Šoltésová Prnová Marta, PhD. |
| SAS cosolvers: | Mgr. Boďo Pavol, PhD., RNDr. Kováčiková Lucia, PhD., Ing. Lepáček Marek, Ing. Štefek Milan, CSc. |
| Annotation: | Increased expression of aldo-keto reductases (AKRs) in tumors of lung, breast, prostate, cervix, testes and colon were reported, and the role of AKRs in the etiology of colorectal carcinoma has been confirmed. Although the AKRs have been studied extensively in the context of diabetic complications, studies in the last decade reveal the role of AKRs in the chemoresistance. The project will focus on the exploration of novel specific targets of chemoresistance represented by the AKRs and will comprise a multidisciplinary approach based on recognition of relevant genetic factors, namely specific mutations that cause chemoresistance, and their relationships to the molecular pathways mediated by AKRs. Moreover combination of QSAR and medicinal chemistry approaches will be used to explore the chemical space of AKR inhibitors with the aim to find the chemical entities of the highest efficacy and selectivity. The project is expected to contribute to establishing personalized therapy of cancer. |
| Ligand induced modulation of calcium pump SERCA – study of mechanism and design of new compounds | |
| Duration: | 1. 1. 2022 - 31. 12. 2025 |
| Evidence number: | 2/0103/22 |
| Program: | VEGA |
| Project leader: | RNDr. Májeková Magdaléna, PhD. |
| SAS cosolvers: | RNDr. Kováčiková Lucia, PhD., Ing. Micháliková Silvia, PhD., Mgr. Rezbáriková Petronela, PhD., Mgr. Šramel Peter, PhD., Mgr. Wetter Erik |
| Annotation: | Calcium signaling plays a crucial role in many physiological processes such as muscle contraction, gene expression, apoptosis and insulin secretion. A primary role in the maintenance of intracellular Ca2+ concentration belongs to SERCA – sarco/endoplasmic reticulum Ca2+-ATPase. As an impaired function of Ca2+-ATPase is associated with various chronic diseases and disorder, the compounds able to restore it are important as potential drugs. Our aim is to elucidate the mechanism of known SERCA activators by means of experimental and theoretical methods and to use this knowledge in design of new compounds, able to maintain SERCA function. In the framework of our research related to diabetes, we plan to include two more targets in our design – inhibition of polyol pathway and oxidation stress. |
| Can the modulation of sarco-endoplasmic Ca2+ - ATPase (SERCA) by selected natural substances be regulated by sirtuins? Importance in supportive treatment of diabetic complications and tumor diseases | |
| Duration: | 1. 1. 2022 - 31. 12. 2025 |
| Evidence number: | 2/0063/22 |
| Program: | VEGA |
| Project leader: | Mgr. Rezbáriková Petronela, PhD. |
| SAS cosolvers: | RNDr. Lomenová Jana, PhD., Ing. Micháliková Silvia, PhD. |
| New methods of treating heart failure. Prevention of oxidative stress by molecular hydrogen. | |
| Duration: | 1. 1. 2022 - 31. 12. 2025 |
| Evidence number: | 2/0092/22 |
| Program: | VEGA |
| Project leader: | RNDr. Kura Branislav, PhD. |
| SAS cosolvers: | Formanková Iveta, Mgr. Kaločayová Barbora, PhD., Kniesová Adela , Mgr. Pavelková Patrícia, D.h.c., Prof., MUDr. Slezák Ján, DrSc., FIACS, Mgr. Šnúriková Denisa, RNDr. Vlkovičová Jana, PhD. |
| Annotation: | Heart failure (HF) globally affects approximately 26 million people worldwide. Despite many therapeutic advances in the symptomatic treatment of HF, the prevalence, mortality and costs associated with treatment in developed countries continue. One of the key mechanisms involved in the development of the pathophysiology of the failing heart is the uncontrolled overproduction of reactive oxygen species, which causes damage to lipids in membranes, mitochondria, proteins and DNA, leading to cell death. Blocking hydroxyl and nitrosyl radicals could therefore prevent the destruction of cellular components and the progression of HF.Recently, it was discovered that molecular hydrogen (H2) has a protective effect in the case of damage to various organs, mainly due to its antioxidant activity. We hypothesize that H2 application could be a new effective treatment for HF patients. The project is aimed at investigating the therapeutic use of H2 and its ability to act cardioprotectively in the isoproterenol-induced HF model in older rats. |
| - | |
| Duration: | 1. 7. 2024 - 31. 12. 2025 |
| Evidence number: | PostdokGrant APD0130 |
| Program: | Iné projekty |
| Project leader: | Mgr. Svetláková (Boťanská) Barbora, PhD. |
| Psychophysiological correlates of semantic interference control | |
| Duration: | 1. 7. 2024 - 31. 12. 2025 |
| Evidence number: | |
| Program: | Iné projekty |
| Project leader: | Mgr. Michalko Drahomír, PhD. |
| Annotation: | The human brain integrates vast amounts of information about the world into organised semantic representations,forming a knowledge basis by which we understand and think about objects and events unfolding in our environment.The hallmark of our cognitive system is the ability to flexibly select from this vast pool of knowledge only those bitsthat suit the current contextual demands, allowing us to adapt our thinking to everchanging conditions. A crucial rolein this ability plays the mechanism of inhibitory control, which shapes our thinking to meet the current situationaldemands by suppressing interfering, contextually irrelevant bits of knowledge. Contemporary findings indicate that thefunctionality of this mechanism is influenced by catecholamines (dopamine and noradrenaline). These accountssuggest that deviations from optimal catecholaminergic signalling disrupt inhibitory control, hindering the ability todiscern relevant from irrelevant bits of knowledge, resulting in aberrant thought patterns and behaviours symptomaticof various neuropsychiatric conditions. In this project, we plan to test these accounts by developing a novelbehavioural method capable of indexing the ability to follow contextual demands under different levels of semanticinterference. Subsequently, we plan to combine this method with physiological measures of dopaminergic(spontaneous eyeblink rate) and noradrenergic (changes in pupil size) activity to evaluate, in a detailed way, howthese systems affect our ability to resolve semantic interference of varying strength. The proposed project maysubstantially improve our understanding of adaptive cognitive processes with high clinical relevance, particularly forpatients with memory and thought control deficits. |
| Study of the role of innate cardioprotection in the rat myocardium evoked by non-pharmacological adaptive stimuli under normal and pathological conditions. | |
| Duration: | 1. 1. 2022 - 31. 12. 2025 |
| Evidence number: | 2/0104/22 |
| Program: | VEGA |
| Project leader: | MUDr. Ravingerová Táňa, DrSc., FIACS |
| SAS cosolvers: | Mgr. Andelová Natália, PhD., prof., PharmDr. Duriš Adameová Adriana, PhD., FIACS, Mgr. Farkašová Veronika, PhD, Ing. Ferko Miroslav, PhD., RNDr. Kura Branislav, PhD., D.h.c., Prof., MUDr. Slezák Ján, DrSc., FIACS |
| Annotation: | Despite advances in pharmacotherapy, interventional cardiology, and surgery, a growth of ischemic heart disease as one of the main reasons for heart failure will not reduce over the next decades. It is due to longer survival aftermyocardial infarction (IM) but gradual impairment of its function and incidence of comorbidities. Attenuation of IM consequences employing ischemic “preconditioning“ (PC) is not commonly used in clinical praxis due to technical requirements and short-term duration. On the other hand, there are other adaptive interventions such as PC in a distant organ, physical activity, and/or chronic or acute hypoxia. Their advantage over classical IPC is anoninvasive, relatively simple, and safe mode of introduction with a possibility of repeated application that may be a prerequisite of greater efficiency in humane medicine. It is assumed that application of noninvasive forms of PC induces similar effects as IPC – activation of cell signaling cascades of endogenous cardioprotection |
| Development of diabetic nephropathy and its treatment with nutraceutic in experimental conditions | |
| Duration: | 1. 1. 2022 - 31. 12. 2025 |
| Evidence number: | 2/0148/22 |
| Program: | VEGA |
| Project leader: | Mgr. Kaločayová Barbora, PhD. |
| SAS cosolvers: | Mgr. Ferenczyová Kristína, PhD., Ing. Kornieieva Daria, Mgr. Kovačičová Ivona, Mgr. Šnúriková Denisa, RNDr. Vlkovičová Jana, PhD. |
| Development of multifunctional aldose reductase inhibitors based on triazinoindoles: Optimization of their biological activity, selectivity, bioavailability and antioxidant properties. | |
| Duration: | 1. 1. 2022 - 31. 12. 2025 |
| Evidence number: | 2/0008/22 |
| Program: | VEGA |
| Project leader: | RNDr. Kováčiková Lucia, PhD. |
| SAS cosolvers: | Mgr. Boďo Pavol, PhD., RNDr. Májeková Magdaléna, PhD., Ing. Šoltésová Prnová Marta, PhD., Mgr. Šramel Peter, PhD., Ing. Štefek Milan, CSc. |
| Annotation: | Aldose reductase inhibitors (ARIs) have been developed as therapeutics for the treatment of diabetic complications, inflammation and some types of cancer associated with chronic inflammation. In our previous projects, we identified derivatives of indol-1-yl acetic acid, 2-(3-thioxo 2H-[1,2,4]triazino[5,6-b]indol-5(3H)-yl)acetic acid (cemtirestat, CMTI) and 2-(3-oxo-2H-[1,2,4]triazino[5,6-b]indol-5(3H)-yl)acetic acid (OTI) as lead structures. Their high inhibitory effect and selectivity, favorable physicochemical parameters and good water solubility render these derivatives as promising candidates for structure optimization. The project focuses on the design and chemical synthesis of new structural analogs by optimizing the 5-carboxymethyltriazinoindole skeleton, in order toincrease inhibitory activity, selectivity, bioavailability, antioxidant activity and improve ADME properties. Theefficacy of the new derivatives will then be evaluated in vitro and ex vivo by a structure-activity relationship (SAR)study. |
| Zofenopril and erucin, H2S releasing coumpounds, in therapy of cardiovascular disorder in experimental model of obesity and 2 type diabetes | |
| Duration: | 1. 1. 2022 - 31. 12. 2025 |
| Evidence number: | 2/0147/22 |
| Program: | VEGA |
| Project leader: | RNDr. Čačányiová Soňa, PhD. |
| SAS cosolvers: | MSc. Aydemir Basak Gunes, Mgr. Berényiová Andrea, PhD., RNDr. Drobná Magdaléna, PhD., Mgr. Golas Samuel, PhD., Ing. Kožík Jozef, Mgr. Zemančíková Anna, PhD. |
| Annotation: | Hydrogen sulfide (H2S) represents an important gaseous transmitter involved in the vascular tone regulation, however, its role in pathological stages such diabetes and obesity remains unexplained. In both, arterial hypertension and metabolic disorder without obesity, H2S produced by arterial wall could participate in impaired vascular function, on the other side, sulfide signal pathway can be a part of compensatory vasoactive mechanisms. We suppose that the escalated metabolic disorder and obesity could impair balanced action of sulfide pathway and enhance the injury of vascular system. H2S-releasing compounds could provide the treatment leading to the decrease of detrimental vasoactive and pro-oxidative effects. We will investigate the chronic effect of angiotensin-converting enzyme inhibitor zofenopril and natural isothiocyanate erucin, both acting as H2S donors, on cardiovascular system of obese Zucker diabetic rats to confirm or refuse a beneficial effect of therapy with H2S releasing drugs in obesity. |
| Identification of stress-induced alterations in expression of NRF2 target genes in rat models of prehypertension: the effect of comorbid hypertriglyceridemia and dimethyl fumarate treatment | |
| Duration: | 1. 8. 2024 - 31. 7. 2025 |
| Evidence number: | 09I03-03-V06-00047 |
| Program: | Plán obnovy EÚ |
| Project leader: | RNDr. Bernátová Iveta, DrSc. |
| Annotation: | The project is a capital booster associated with the APVV-22-0296 project to support infrastructure purchase. |
| Effects of mesenchymal stem cells and HMGB1 inhibitor on cardiovascular system after experimentally induced myocardial infarction in hypertension and diabetes mellitus | |
| Duration: | 1. 8. 2024 - 31. 7. 2025 |
| Evidence number: | 09I03-03-V06-00059 |
| Program: | Plán obnovy EÚ |
| Project leader: | RNDr. Cebová Martina, PhD. |
| ACE2MAS - Cardiometabolic effects of Mas receptor stimulation by modulation of the renin-angiotensin system - the key role of angiotensin-converting enzyme 2 | |
| Duration: | 1. 7. 2021 - 30. 6. 2025 |
| Evidence number: | APVV-20-0421 |
| Program: | APVV |
| Project leader: | RNDr. Čačányiová Soňa, PhD. |
| SAS cosolvers: | Mgr. Golas Samuel, PhD. |
| Annotation: | The renin-angiotensin system (RAS) is a hormonal cascade whose chronic activation contributes to the development of cardiovascular pathologies caused mainly by remodeling of the heart and blood vessels. It is becoming apparent that the benefit of RAS inhibitors includes, in addition to Ang II inhibition, stimulation of the alternative arm of RAS mediated by the ACE2/Ang1-7/Mas receptor, which has vasodilatory, antiproliferative, antiinflammatory and metabolic effects. The aim of the present project will be to compare the effect of ACE inhibition, AT1 blockade, stimulation of ACE2 (diminazene) and Mas receptor (cyclic Ang1-7, alamandine) in a model of old, obese, diabetic hypertensive Zucker rats with a focus on the potential benefit of Ang1-7/Ang1-5 on glucose utilization, insulin signal transduction, reduction of the inflammatory response and function of the cardiovascular system. Given the potentially key role of RAS and especially ACE2 in the development of acute respiratory distress syndrome (ARDS) and the severe course of COVID-19, the aim of the present project will be to detect changes in membrane and serum ACE2 and expression of other key molecules for viral infection (ADAM17, TMPRSS2, furin and B0AT1 transporter) using various pharmacological interventions. The dependence of the putative alterations on the activity of the Mas receptor will be monitored by its specific antagonist A779. In vitro, following treatment of human alveolar cells and adipocyte cultures with RAS and diminazene inhibitors, the changes in the ability to bind SARS-CoV-2 virus will be assessed using a pseudoviral methodology. The obtained results might contribute to the elucidation of the role of ACE2 and Mas receptor in the pathogenesis of obesity and diabetes. The project might also contribute to the clarification of the choice of an effective RAS inhibitor in the elderly with a combination of hypertension, obesity and diabetes. |
| NEKDIAKAR - Necroptotic and pleiotropic effects of RIP3 kinase acting as a convergent point in cardiac cell loss: understanding the basic mechanisms in the ischemic heart with or without metabolic stress as a tool for designing therapeutic approaches. | |
| Duration: | 1. 7. 2021 - 30. 6. 2025 |
| Evidence number: | APVV-20-0242 |
| Program: | APVV |
| Project leader: | MUDr. Ravingerová Táňa, DrSc., FIACS |
| SAS cosolvers: | doc. RNDr. Barteková Monika, PhD., Mgr. Farkašová Veronika, PhD, Mgr. Ferenczyová Kristína, PhD., Mgr. Kindernay Lucia, PhD. |
| Annotation: | Necroptosis, which has been found in ischemic heart, seems to be a significant factor in the body\'s fate. Themechanisms responsible for execution of this cell death are not fully elucidated and the canonical RIP1-RIP3-MLKLpathway does not appear to be the only one responsible for such cell loss. We suggested a dual pronecroptoticand proinflammatory role of RIP3 in the pathogenesis of post-infarction heart failure. In addition, we have indications on other pleiotropic action of RIP3 being associated with oxidative stress, as well as affectingmitochondrial activity and dynamics. Thus, it appears that RIP3, but not RIP1, may be a key node in intracellularsignaling. The proposed processes in the heart damaged by ischemia and reperfusion need to be examined in detail and it is also necessary to determine whether RIP3 inhibition is able to limit these processes and thusalleviate cardiac dysfunction and remodeling. A considerable originality of the project is the study of necroptosis in a metabolically-stressed heart due to diabetes and its precursor - prediabetes and its contribution to heart damage. We will investigate the canonical and the newly-proposed RIP3-mediated signaling and evaluate their activation depending on the glucose levels and other biochemical characteristics of these disturbances in glucose metabolism. We hypothesize that antidiabetic therapy is able to mitigate heart damage due to the limitation of necroptosis what is further amplified by antinecroptotic agents. An important concept is the assessment of released markers of necroptosis signaling into the circulation which could be a prognostic and diagnostic approach. Proposed studies and a variety of methodological approaches, employed according to the guideline for the evaluation of necroptosis in the heart, will provide innovative insights into the pathogenesis of prediabetic and diabetic heart and its damage due to ischemia, and thereby indicate a significant pharmacotherapeutic target. |
| StrokeRehab - Novel approach to post-stroke rehabilitation. A basic and translational study, aiming to restore posture control and body symmetry in post-stroke patients by sensory stimulation. | |
| Duration: | 1. 8. 2021 - 30. 6. 2025 |
| Evidence number: | APVV-20-0420 |
| Program: | APVV |
| Project leader: | RNDr. Bzdúšková Diana, PhD. |
| SAS cosolvers: | Mgr. Hirjaková Zuzana, PhD., RNDr. Kimijanová Jana, PhD., Mgr. Marko Martin, PhD., MUDr. Riečanský Igor, PhD., Mgr. Rovný Rastislav, Prof. MUDr. Valkovič Peter, PhD. |
| Annotation: | The main goal of this project is to investigate the pathophysiological mechanisms of keeping balance while sitting and standing in post-stroke patients and to define the rationale for interventions based on visual and proprioceptive stimulations for enhancing balance, impaired trunk mobility and trunk asymmetry. To achieve this, we will use the original method for rehabilitation and monitoring of patients as well as specialized devices together with softwares which we developed during our previous project APVV-16-0233. Stroke is a major health problem, especially considering that post-stroke patients typically have residual impairments to their motor and sensory functions directly affecting their postural system. Keeping balance while sitting up in bed or on a chair is with high probability the first thing a therapist addresses to patients. Controlled trunk function is an important and essential component for standing balance, gait and other daily activities. The voluntary movements of the trunk clearly reveal the postural and movement asymmetry of the upper part of the body. The asymmetric position is most often characterized by one-sided tilt of the trunk or its reduced mobility to one side. We aim to advance knowledge on the abnormal posture due to impairment of dynamic balance as a consequence of stroke, and to exploit visual and proprioceptive stimulations in order to improve posture and trunk asymmetry in post-stroke patients. Finally we will evaluate efficiency of rehabilitation procedures using two different approaches: i) by recording of the centre of pressure using force plate and ii) by recording of trunk tilts using inertial sensors. |
| HHTgINFL - The role of inflammation in the development of cardiovascular complications associated with metabolic syndrome and prediabetes | |
| Duration: | 1. 7. 2022 - 30. 6. 2025 |
| Evidence number: | SK-CZ-RD-21-0102 |
| Program: | APVV |
| Project leader: | RNDr. Čačányiová Soňa, PhD. |
| SAS cosolvers: | MSc. Aydemir Basak Gunes, Mgr. Berényiová Andrea, PhD., RNDr. Cebová Martina, PhD., RNDr. Drobná Magdaléna, PhD., Mgr. Golas Samuel, PhD. |
| Annotation: | Inflammatory conditions are one of the most important pathophysiological factors in the development of cardiovascular diseases. Perivascular adipose tissue (PVAT), its pro-inflammatory activities and its impact on vasoactive functions may play an important role in the development of cardiovascular complications. Moreover, impaired PVAT function leads to the secretion of proinflammatory factors and endothelial dysfunction which could be associated with unbalance in sulfide signaling. The aim of the proposed project will analyze the vasoactive and inflammatory mechanisms in the vessel wall and PVAT with special attention to sulfide signaling in model of metabolic syndrome. Crosstalk among them occurs, but the exact mechanism is unknown. The pro-inflammatory mechanisms are particularly triggered in the early stage of diabetes and metabolic syndrome, therefore, a unique model of prediabetes and metabolic syndrome, hereditary hypertriglyceridemic rats, will be used. Currently, increased attention is focused on aspects of personalized medicine, which can contribute to more effective therapy through precise targeting of a specifically defined group of patients.The development of cardiovascular complications and diabetes may depend on age, reproductive status, and genetic background. Cardiovascular riskis significantly increased in postmenopausal women, while it is lower in women under 40 than in men of the same age. The project will monitor the effect of gender and reproductive status in female rats after surgical ovariectomy to reveal possible differences in the mechanism of cardiovascular disorders and to help to better specify therapeutic targets appropriate to non-obese prediabetic postmenopausal women. In the next part, the project will investigate the possible beneficial effects of the administration of the bioflavonoid troxerutin in lowering the risk of developing cardiovascular complications associated with postmenopausal metabolic syndrome. |
| Multi-Glu - Multi-target approach to diverse molecular mechanisms of diabetic complications and other glucose toxicity related diseases | |
| Duration: | 1. 8. 2021 - 30. 6. 2025 |
| Evidence number: | APVV-20-0534 |
| Program: | APVV |
| Project leader: | RNDr. Májeková Magdaléna, PhD. |
| SAS cosolvers: | Mgr. Benešová Barbora, Mgr. Boďo Pavol, PhD., Mgr. Heger Vladimír, PhD., RNDr. Kováčiková Lucia, PhD., RNDr. Lomenová Jana, PhD., Ing. Micháliková Silvia, PhD., Mgr. Rezbáriková Petronela, PhD., Ing. Šoltésová Prnová Marta, PhD., Mgr. Šramel Peter, PhD., Ing. Štefek Milan, CSc., Mgr. Wetter Erik |
| Annotation: | Diabetes mellitus and other diseases related to the glucose toxicity have multifactorial character comprised ofmultiple mechanisms. Besides others, the mechanisms include increased polyol pathway activity, non-enzymaticglycations of proteins, hexosamine pathway, altered protein kinase C activity, oxidation stress and impairedcalcium signaling. Targeting individual mechanisms could lead to design of new compounds - potential drugs for atreatment of diabetic complications. Our aim is to elucidate the impact and roles of individual mechanisms. In thisendeavor, we will build upon our previous results, which brought a new insight in details of polyols pathwaymechanisms by means of the study of cemtirestat and other novel compounds designed by our group. |
| AMVADYMESE - Significance of endothelial alpha 1 AMPK for vascular dysfunction and metabolic senescence in a rat model of metabolic syndrome/diabetes mellitus type II | |
| Duration: | 1. 7. 2022 - 30. 6. 2025 |
| Evidence number: | 1368/03/02 |
| Program: | SASPRO |
| Project leader: | Ing. Kvandová Miroslava, PhD. |
| Annotation: | Endothelial dysfunction is an early common feature of many cardiovascular diseases, caused by decreased nitric oxide (NO) production and/or increased NO inactivation due to oxidative stress. This influences a patient\'s risk of future cardiovascular events1. The overall goal is to improve primary and secondary prevention for cardiovascular diseases. Therefore, analyzing key factors that prevent or positively influence endothelial dysfunction is essential. Working group of prof. Münzel/Daiber (current affiliation) has been focused on the role of AMP-dependent protein kinase (AMPK) for several years. This ubiquitously expressed enzyme is the central energy sensor of cells in the cardiovascular system2. The protective effect of AMPK has been already demonstrated, especially its protective properties on endothelial function, oxidative stress, cell aging, and inflammation3,4. In addition, AMPK regulates many metabolic pathways that are disturbed in the context of diabetes mellitus, such as the activation of glucose transport in skeletal muscle or the inhibition of gluconeogenesis in the liver. These properties suggest that AMPK may improve diabetic metabolic control. It has been shown for diabetes mellitus that vascular changes are prognostically decisive5. Despite enormous research, the molecular changes that lead to endothelial dysfunction and predisposition to cardiovascular diseases due to α1AMPK-related dysregulation are insufficiently known. Therefore, the following questions will be addressed:1. How do α1AMPK influence endothelial function, formation of reactive oxygen species, and vascular inflammation in the rat model of the metabolic syndrome/diabetes mellitus II type?2. Exploring the role of α1AMPK expression in endothelial cell death and the development of metabolic senescence in hyperglycemia and diabetes?3. Are metabolic syndrome/diabetes mellitus II type mediated disorders of the endothelial function associated with the gender-specific regulation of alpha 1 AMPK? |
| The relationship between cytokines and connexin-43 in brown adipose tissue in laboratory rats with increased thermogenesis. | |
| Duration: | 1. 7. 2024 - 30. 6. 2025 |
| Evidence number: | |
| Program: | Iné projekty |
| Project leader: | RNDr. Egan Beňová Tamara, PhD. |