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Cardiovascular and metabolic research group

Members:
Péter Ferdinandy, M.D., D.Sc., Head of Department, group leader
Pál Pacher, M.D.,PhD. consultant
Huba Kalász, D.Sc., consultant
Valeria Kecskeméti, M.D., Ph.D., professor emerita
Andrea Szebeni, M.D., Ph.D., assistant professor
Zoltan Giricz, Pharm.D., Ph.D., senior research associate
Zoltan Varga, M.D., PhD,  junior research associate
Anikó Görbe, M.D., PhD, associate professor
Éva Sághy, M.D., PhD, assistant professor
Bence Ágg, Ph.D. student

András Makkos, Ph.D student
Gábor Koncsos, Ph.D. student
Csilla Nagy, Ph.D. student
Gábor Brenner, M.D.

Tünde Petrovics, labmanager
Benkes Jenőné, laboratory assistants

Projects

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.

Studying the role of extracellular vesicles in cardioprotective mechanisms

Investigation of the role of extracellular vesicles in cardioprotective mechanisms: Remote ischemic condtitioning is a well-known entity among cardioprotective mechanisms. Remote ischemic conditioning could be achieved by repetitive ischemia of any distant organ (e.g. lower limb) inducing cardioprotection. Our research group investigates the protective effects of extracellular vesicles released from the ischemic lower limb. microRNA and protein content of the vesicles are also examined for novel therapeutic and diagnostic targets, which could be applied in clinical settings in the future.

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

Main cooperators:
•  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