GENE EXPRESSION PROFILING IN RAT LEFT VENTRICLE AFTER 10-WEEK MILD EXERCISE TRAINING

Whereas physical exercise is a known protective factor against cardiovascular morbidity and mortality, the effects of mild exercise (as recommended to most adult humans for cardiovascular fitness) are less clear and the underlying molecular mechanisms still remain to be explored. To identify the gene expression changes involved in the induction of this phenotype, a genomic approach was used in an animal model known to induce cardioprotection. Rats were trained at moderate intensity on a treadmill: 25 m/min, 10% incline, 1 h/day, 3 days/week, 10 weeks; about 60% of the maximal aerobic power. By Affymetrix technology, we investigated gene expression profile induced by exercise training in left ventricle (LV) of trained (n = 10) and control (n = 10) rats. This exercise protocol did not induce cardiac hypertrophy and determined decreased infarct size (p = 0.02) after ischemia/reperfusion experiments. Rats were sacrificed 48 hours after the last training session, in order to identify long-lasting changes in gene expression. We observed 10 genes differentially expressed in LV of exercised animals with respect to controls and 2 gene sets associated with training. We validated by real-time PCR the upregulation of three genes: caveolin 3, beta enolase, and hypoxia inducible factor 1 alpha. Moreover, caveolin 3 protein levels resulted higher in exercised rats than in controls by immunohistochemistry and Western Blot analysis. Our data indicate that Cav3, Eno3, Cyp27a1, Egln1, Cst3 and Tnfaip1 genes as well as GABA and ARENRF2 pathways show long-lasting expression changes in rat LV as a consequence of mild exercise training associated to cardioprotection without induction of hypertrophy.