Abstract 1273: Anti-oxidative Effects of Exercise Training Promote the Survival of c-kit+ Cardiac Progenitor Cells and Endogenous Myocardial Repair in Chronic Heart Failure
Exercise training (ET) partially reverses left ventricular remodeling and enhances ejection fraction (EF) in chronic heart failure (CHF). The discovery of cardiac progenitor cells (CPCs) offers the possibility that the encouraging effects of ET on left ventricular performance might result from CPC-mediated myocardial self-renewal. Therefore, we aimed to determine, whether ET modulates the myocardial microenvironment to promote activation of c-kit+ CPCs, and whether this is associated with a recovery of EF in a model of CHF.
Methods: Male Wistar rats were sham-operated (Sham) or underwent LAD ligation (CHF). After three weeks, animals of both groups were subjected to an inactive control group (Sham-C, n=12; CHF-C, n=12) or a training group (Sham-T, n=12; CHF-T, n=12). Rats in the training groups were running on a treadmill one hour daily for a period of 4 weeks. The number of surviving c-kit+ CPCs and surviving myocyte lineage-committed c-kit+/MEF2+ CPCs in the infarcted heart and the remote myocardium were recognized by immunohistochemistry (number of cells per mm2, MEF2: myocyte enhancer factor 2). Hemodynamics were determined by echocardiography and conductance catheter.
Results: In CHF-C, myocardial expression of angiotensin II was increased by 178%, which was associated with an excessive production of reactive oxygen species by the NAD(P)H oxidase and consequently death of CPCs by apoptosis. In CHF-T, ET normalized myocardial angiotensin II content and NAD(P)H oxidase activity thereby improving the survival of CPCs, which had migrated into the infarcted area to reconstitute the damaged heart. These effects of ET were linked to a gain in ejection fraction by 25 % and a decrease in end-diastolic diameter by 28 % in CHF-T.
Conclusion: In CHF, anti-oxidative effects of ET promote the survival and differentiation of c-kit+ CPCs in the heart. This is associated with an improvement in left ventricular performance and reversal of adverse ventricular remodeling.