Gene expression profile of rat left ventricles reveals persisting changes following chronic mild exercise protocol: implications for cardioprotection

Abstract

BackgroundEpidemiological studies showed that physical exercise, specifically moderate lifelong training, is protective against cardiovascular morbidity and mortality. Most experimental work has focused into the effects and molecular mechanisms underlying intense, rather than mild exercise, by exploring the acute effect of training. Our study aims at investigating the cardioprotective effect of mild chronic exercise training and the gene expression profile changes at 48 hrs after the exercise cessation. Rats were trained at mild intensity on a treadmill: 25 m/min, 10%incline, 1 h/day, 3 days/week, 10 weeks; about 60% of the maximum aerobic power. By Affymetrix technology, we investigated the gene expression profile induced by exercise training in the left ventricle (LV) of trained (n = 10) and control (n = 10) rats. Cardioprotection was investigated by ischemia/reperfusion experiments (n = 10 trained vs. n = 10 control rats).ResultsMild exercise did not induce cardiac hypertrophy and was cardioprotective as demonstrated by the decreased infarct size (p = 0.02) after ischemia/reperfusion experiments in trained with respect to control rats. Ten genes and 2 gene sets (two pathways) resulted altered in LV of exercised animals with respect to controls. We validated by real-time PCR the increased expression of four genes: similar to C11orf17 protein (RGD1306959), caveolin 3, enolase 3, and hypoxia inducible factor 1 alpha. Moreover, caveolin 3 protein levels were higher in exercised than control rats by immunohistochemistry and Western Blot analysis. Interestingly, the predicted gene similar to C11orf17 protein (RGD1306959) was significantly increased by exercise. This gene has a high homology with the human C11orf17 (alias: protein kinase-A interacting protein 1 or breast cancer associated gene 3). This is the first evidence that this gene is involved in the response to the exercise training.ConclusionOur data indicated that few, but significant, genes characterize the gene expression profile of the rat LV, when examined 48 hrs since the last training section and that mild exercise training determines cardioprotection without the induction of hypertrophy.

A kinase interacting protein (AKIP1) is a key regulator of cardiac stress

“…Exercise has been shown to mimic ischemic preconditioning and also lead to cardiac protection (38). Gene expression profiles of rat left ventricles after mild exercise showed elevated mRNA levels of cAMP response element binding protein (plausibly PKA-regulated), AKIP1, and HIF1α (39). Such findings are consistent with our observations and suggest that overexpression of AKIP1 may be a therapeutic approach for limiting cardiac injury.…”

Electrophysiology and metabolism of caveolin-3-overexpressing mice

“…Our data suggests that caveolins may be an intrinsic factor involved in the cardiac response to exercise via their multiple interactions with ion channels and other cell signaling molecules. Previous investigations have shown that Cav-3 mRNA is up regulated in trained animal hearts approximately 2-fold [18]. Interestingly, our Cav-3 OE mice have an approximate 2-fold elevation of Cav-3 protein at baseline [55].…”

Hypoxia inducible factor 1 (HIF-1) and cardioprotection

“…The possible involvement of HIF-1 in exercise-induced cardioprotection was recently demonstrated by Giusti et al [66] . In a rat model of chronic exercise-induced cardioprotection, these researchers found that HIF-1α was among the genes that were significantly upregulated in the left ventricular tissues 48 hours after the last training session of the 10-week mild intensity aerobic exercise protocol.…”

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