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Identification of cardioprotective targets in ischemic heart disease and its comorbidities

Investigation of the role of neuropeptides in cardioprotection in in vitro and in vivo systems

Ischemic heart disesses are the leading cause of death wordwide. Currently there are no cardioprotective drugs on the market, which could limit the myocardial infarct size, therefore identification of cardioprotective mediators and drug targets are an urgent need. Neuropeptides released from the sensory nerve terminals (e.g. CGRP) were shown to play a role in the cardioprotective effect of ischemic preconditioning but the role of  neuropeptides in cardioprotection and therapeutical potencial are still unknown. Our aim is to investigate the role of neuropeptides in cardioprotection using in vitro and in vivo systems.

Investigations on cardiomyocytes: Fig. 1.: Simulated ischemia/reperfusion (SI/R) experiment

Learning opportunities: cell culture methods, SI/R experiments, viability test, in vitro methods: Western blot, PCR, ELISA, histology

Project leader: Dr. Éva Sághy assistant professor, Dr. Imre Vörös PhD student

Identification of drug targets for ischemic heart disease with bioinformatic target prediction followed by experimental validaton of predicted targets

There is no available cardioprotective drug on the market that could reduce the infarct size, mainly because of the hypothesis-driven, biased methodology of drug target identification and the lack of comorbidty models during the drug development. Our aim is to overcome the limitations of the standard hypothesis driven approaches by analysing tarnscriptomics data from comorbidity models. Based on the expression profiles here we predict potential molecular drug targets by in silico methods and validate the predicted targets.Fig 2.: Workflow

Publication in the field:

  • Varga ZV, Giricz Z, Bencsik P, Madonna R, Gyongyosi M, Schulz R, Mayr M, Thum T, Puskas LG, Ferdinandy P. Functional Genomics of Cardioprotection by Ischemic Conditioning and the Influence of Comorbid Conditions: Implications in Target Identification. Curr Drug Targets. 2015;16(8):904-11.
  • Varga ZV, Zvara A, Faragó N, Kocsis GF, Pipicz M, Gáspár R, Bencsik P, Görbe A, Csonka C, Puskás LG, Thum T, Csont T, Ferdinandy P. MicroRNAs associated with ischemia-reperfusion injury and cardioprotection by ischemic pre- and postconditioning: protectomiRs. Am J Physiol Heart Circ Physiol. 2014 Jul 15;307(2):H216-27.
  • Giricz Z, Varga ZV, Baranyai T, Sipos P, Pálóczi K, Kittel Á, Buzás EI, Ferdinandy P. Cardioprotection by remote ischemic preconditioning of the rat heart is mediated by extracellular vesicles. J Mol Cell Cardiol. 2014 Mar; 68:75-8.
  • Ágg B, Baranyai T, Makkos A, Vető B, Faragó N, Zvara Á, Giricz Z, Veres DV, Csermely P, Arányi T, Puskás LG, Varga ZV, Ferdinandy P. MicroRNA interactome analysis predicts post-transcriptional regulation of ADRB2 and PPP3R1 in the hypercholesterolemic myocardium. Sci Rep. 2018 Jul 4;8(1):10134.

Learning opportunities: in vitro methods: Western blot, PCR, cell culture methods

Project leader: Dr. Éva Sághy assistant professor, Dr. Imre Vörös PhD student, Dr. Bernadett Kiss PhD student