FP6 priority

1.1.1   Genomics and Biotechnology for Health

1.1.2.1
1.1.1

Title of the proposal

Adaptation of the heart to stress: a novel strategy in management of cardiovascular diseases and diabetes

Institute

Slovak Academy of Sciences, Institute for Heart Research
Dubravska cesta 9, 842 33 Bratislava, Slovak Republic

Contact

Research subject for a potential FP6 project

A new concept of the cardioprotection against ischemic injury is based on the exploitation of the heart’s own protective mechanisms activated by a mild cellular stress (e.g., brief ischemia or oxidative stress) followed by adaptive response of cardiac cells resulting in increased ischemic tolerance of the heart. Mechanisms of short-term or chronic cardiac adaptation (e.g., to chronic myocardial hypoxia and remodelling) involve activation of cell signalling system, from the cell receptors, postreceptor pathways (protein kinases cascades), up to potential end-effector mechanisms, e.g., ATP-dependent K+ channels [K(ATP)] in the heart mitochondria, and include changes in gene expression and synthesis of some cytoprotectibe proteins. It is likely that different mitogen-activated protein kinase (MAPKs) cascades mediate response of cardiomyocytes to stress with the final effect on transcriptional activity and expression of genes. Pharmacological modulations of MAPKs activity, as well as gene-targeting and in this way mediated activation or inactivation of specific MAPKs help to elucidate the real biological role of MAPK signalling cascades in cardiac pathology and cardioprotection. The aims of the project are: i. to study molecular mechanisms of various forms of adaptive processes in the normal and pathologically altered (diabetic) heart; ii. to identify common mechanisms of cardioprotection during adaptation of the heart to various forms of stress, with a special regard to the differential role of MAPKs and activation of mitochondrial K(ATP) channels; iii. to investigate a link between the above processes. The anticipated results are expected to extend our knowledge of the basic pathophysiological mechanisms of myocardial adaptation and to contribute to the development of new alternative approaches to combat cardiovascular diseases and diabetes

Recent international cooperation of the research team

Institute of Physiology, AS CR, Prague, Czech Republic;
Max-Planck Institute of Physiology, Bad Nauheim, Germany

Proposer´s relevant publications related to the research subject

1. Ravingerova T., Neckar J., Kolar F., Stetka R., Volkovova K., Ziegelhoffer A., Styk J. Ventricular arrhythmias following coronary artery occlusion in rats: Is diabetic heart less or more sensitive to ischemia? Basic Res Cardiol, 2001, 96(2):160-168.
2. Ravingerova T, Barancik M, Pancza D, Styk J, Ziegelhoffer A, Schaper W, Slezak J. Contribution to the factors involved in the protective effect of ischemic preconditioning. The role of catecholamines and protein kinase C. Ann N Y Acad Sci. 1996 Sep 30;793:43-53.
3. Ravingerova T, Pyne NJ, Parratt JR. Ischaemic preconditioning in the rat heart: the role of G-proteins and adrenergic stimulation. Mol Cell Biochem. 1995 Jun 7-21;147(1-2):123-8.
4. Barancik M., Htun P., Strohm C., Kilian S., Schaper W.: Inhibition of p38-MAPK pathway by a specific inhibitor, SB203580, protects the myocardium against ischemia. J. Cardiovasc. Pharmacology 2000, 35, 474-483