heart failure; signal pathways; epigenetics; transcriptional factors; miRNAs
Explanted human heart, cell lines, patient samples (blood, plasma, tissue), experimental animal models of cardiovascular diseases, Hypertension, diabetes mellitus, cardiac hypertrophy and schema, heart failure
Gene expression (RT-PCR, Western blotting), histology and morphology, confocal microscopy, cell cultivation, cytometry, pharmacological assays, biochemistry assays, isolated organs, in situ cardiovascular fysiology.
We participate in the heart transplantation program, cell based therapy of advanced critical limb ischemia and myocardium after infarction at The National Institute of Cardiovascular Diseases NUSCH a.s. International cooperation: Prof. Wilhem Schimtz, Prof. Frank Muller: Instutute Pharmackologie und Toxikologie, Munster Universitet, Germany Prof. Balwant Tuana, Dept. Molecular Medicine, Ottawa University, Canada Prof.. Robert H. Henning, Dept. Pharmacology, Univerzity of Gronningen, Holland Prof. Peter Ferdinandy, Dept. Pharmacology, Faculty of Medicine, Semmelweis University, Budapest, Hungary
Proposal of project There are several challenges to the translation of these new findings into cardiac regenerative therapies. The proposed project is focused to evaluation the possible specific synergic pharmacological intervention to signal pathways of epigenetics and transcriptional factors and miRNAs in heart failure: - response for activation of foetal gene program, myosine switching and/or hypertrophy process to inhibit the pathoethiology of heart failure, - reprogram of cardiac fibroblasts into cardiac-like myocytes in pathological dysregualted myocardium and exert their effects on the heart regenerat ion, - potentiation molecular signals of paracrine activity of multipotent autotransplanted bone marrow derivates that control and regulate regenerative healing of myocardium. In this project we plane to develop the research in the preclinical stage, just before proceeding to a clinical stage. Based on the outcomes of pervious phases and taking into account the general situation of research related to regenerative medicine, we are especially promoting research using human stem cells and related research and development, the outcomes of which will directly contribute to the benefits therapy of cardiovascular diseases.