- Studies on the role of extracellular vesicles
- Studying the role of EVs in cardioprotective interventions
- Studying the role of EVs in metabolic co-morbidities of cardiac diseases
- Studying the role of EVs in ischemic conditioning
- Studies on the mechanisms and therapies of the cardiac ischemia/reperfusion injury
- Effects of pharmacons on cardiac ischemia/reperfusion injury: hidden cardiotoxicity
- Effect of metabolic comorbidities (diabetes, hypercholesterolemia, etc.) on cardioprotective interventions against ischemia/reperfusion injury
- Utilization and development of network theoretical and bioinformatics methodologies in the research of cardiovascular diseases and pharmacovigilance
- Unbiased network theoretic microRNA interactome analysis for the prediction of most probable targets of differentially expressed microRNAs in cardiovascular diseases
- Applying network theory models on adverse drug event datasets in order to identify novel cardiovascular effects of marketed drugs
- Identification of cardioprotective mikroRNAs and their utilization in the treatment of acute ischemia in small and large animal models
MicroRNAs (20-15 base-long non-coding RNAs) are crucial for numerous biological and pathological processes. In ischemia expression of several miRNAs are altered (e.g. miRNA-21), and thus the protein expression pattern of the heart is thoroughly influenced. Previously we found that overexpression (microRNA-139-5p, microRNA-125b*) or suppression (microRNA-487b) of certain miRNAs induce cardioprotection in isolated cardiomyocytes. Therefore, it is plausible that other miRNAs might also play a role in various forms of cardioprotection. In these investigations we will identify miRNAs that are involved in clinically relevant cardioprotective interventions (e.g. ishcemic postconditioning or remote ischemic perconditioning) in rodent and large animal models of acute ischemia/reperfusion injury. Furthermore, based on our findings we will develop a novel therapeutic strategy that involves miRNA-modulation.
- Signalling and pharmacological modulation of ischemic cardiovascular diseases developing in the background of metabolic derangements
Metabolic syndrome is a common risk of cardiovascular diseases. It is well known that a healthy heart can adapt to ischemic stress, however metabolic syndrome has negative effect on the tolerance of the heart. Our research group has aimed to investigate the pharmacologically relevant signaling pathways, which may connected with the altered tolerance of the heart. The foci of our research are cardioprotective mechnisms by intracellular (auto- and mitophagy) and extracellular (exosomes, microvesicles) vesicles. Our previous studies showed that autophagy/mitophagy was inhibited under hyperlipidemic conditions but the status of mitophagy in the metabolic syndrome is not well known. Our hypothesis was that impaired mitophagy and mitochondrial quality control may contribute to increased cardiovascular risk in metabolic syndrome. Therefore, we investigate the above mentioned mechanisms in several metabolic disease models including diabetes, obesity and metabolic syndrome in rats.
- Developing a network model for the gene expression and signalling pathways of the cardiovascular system and its utilization in the development of therapies against ischemic cardiovascular diseases
Numerous changes have been identified in several signalling pathways in ischemic heart diseases and in cardioprotective mechanisms. However, so far these changes have not been investigated by biological network analysis methods. Therefore, establishing and analysing system-wide network models may help us identify certain molecules or pathways with key roles in ischemic diseases, and cardioprotective mechanisms. Then modulating such elements may result in more efficient therapies against the investigated diseases. Furthermore, the network approach may uncover novel diagnostic markers, which might indicate the extent of cardioprotection more reliably than current parameters. To reach these goals we collect system-wide information with high throughout methods in several projects. Based on these dataset we are developing computer models of changes in biological networks in ischemic heart diseases and in cardioprotective interventions.
Main models and methods:
• Ex vivo heart perfusion systems
• Intracellular microelectrodes for electrophysiological measurements in in vitro atrial and ventricular papillar muscle samples.
• In vivo myocardial infarct and heart failure models
• In vivo models of diabetes and dyslipidemia
• Separation methods: capillary electrophoresis, HPLC-UV, HPLC-ECD, HPLC-MS
• University of Szeged, Department of Biochemistry, Cardiovascular Research Group
• San Diego State University, Donald P. Shiley Bioscience Center, San Diego, CA, USA
• University of Debrecen, Department of Physiology
• Florida International University, Department of Pharmacology, Miami, FL, USA
• University of United Arab Emirates, AlAin, United Arab Emirates
• University of Defence, Department of Toxicology, Hradec Králové, Czech Republic
• University of Szeged, Department of Pharmacology