Mild exercise training, cardioprotection and stress genes profile

Abstract

To improve current knowledge of the molecular mechanisms underlying exercise-induced cardioprotection in a rat model of mild exercise training, Sprague-Dawley rats were trained to run on a treadmill up to 55% of their maximal oxygen uptake for 1 h/day, 3 days/week, 14 weeks, with age-matched sedentary controls (n = 20/group). Rats were sacriWced 48 h after the last training session. Despite lack of cardiac hypertrophy, training decreased blood hemoglobin (7.94 § 0.21 mM vs. 8.78 § 0.23 mM, mean § SE, P = 0.01) and increased both plasma malondialdehyde (0.139 § 0.005 mM vs. 0.085 § 0.009 mM, P = 0.05) and the activity of Mn-superoxide dismutase (11.6 § 0.6 vs. 16.5 § 1.6 mU/ g, P = 0.01), whereas total superoxide dismutase activity was unaVected. When subjected to 30-min ischemia followed by 90-min reperfusion, hearts from trained rats (n = 5) displayed reduced infarct size as compared to controls (37.26 § 0.92% vs. 49.09 § 2.11% of risk area, P = 0.04). The biochemical analyses in the myocardium, which included gene expression proWles, realtime PCR, Western blot and determination of enzymatic activity, showed training-induced upregulation of the following mRNAs and/or proteins: growtharrest and DNA-damage induced 153 (GADD153/ CHOP), heme-oxygenase-1 (HO-1), cyclooxygenase-2 (Cox-2), heat-shock protein 70/72 (HSP70/72), whereas heat-shock protein 60 (HSP60) and glucoseregulated protein 75 (GRP75) were decreased. As a whole, these data indicate that mild exercise training activates a second window of myocardial protection against ischemia/reperfusion by upregulating a number of protective genes, thereby warranting further investigation in man.

Effects of Different Levels of Exercise Volume on Endothelium-Dependent Vasodilation: Roles of Nitric Oxide Synthase and Heme Oxygenase

“…Although elevation of HO mRNA and protein were reported in the rat cardiovascular system after exercise (15,16), to the best of our knowledge, the present study is the first report demonstrating exerciseinduced increases in vascular HO-1 and HO-2 with enhancement in HO-related vasorelaxation. We also found that high volume intens exercise led to hypertension and impairment of endothelium-dependent vascular relaxation, with marked and diffuse increases in eNOS and iNOS across three aortic layers.…”

Partial persistence of exercise-induced myocardial angiogenesis following 4-week detraining in the rat

“…Moderate exercise training shares some of the signaling pathways (Hearse 1994) and most of the induced array of antioxidant and protective molecules (Yellon and Downey 2003;Marini et al 2007) with other preconditioning stimuli, such as repeated bursts of intense physical exercise. The results presented here show that, at variance with such stimuli, moderate exercise training also induces some anatomical adaptations to the increased need for oxygen supply, which may be relevant in providing cardioprotection even at a distant time from the training sessions.…”

“…Total RNA was prepared after Trizol™ (Invitrogen) extraction from frozen left ventricle tissue and quality controlled, as previously described (Marini et al 2007). Real-time RT-PCR was performed in an ABI PRISM 5700 real-time thermal cycler using the SYBR Green kit (Qiagen) and by normalizing to the housekeeping gene RPL13a.…”

“…Exercise training oVsets many age-related gene expression changes (Bronikowski et al 2003;Iemitsu et al 2006), upregulates a number of cardioprotective and anti-oxidant proteins (Powers et al 2004, Marini et al 2007, improves contractile function and optimizes energy usage (Ventura-Clapier et al 2007). Moreover, exercise increases the need for oxygen supply in the cardiac muscle, which may be met by the induction of neo-angiogenetic and vascular remodeling processes (White et al 1998;Brown 2003); these, in turn, may trigger prevention of the adverse eVects of coronary artery stenosis and occlusion (Schaper and Ito 1996).…”

“…To start investigating this issue, we used an in vivo model whereby rats were moderately trained (10 weeks, »60% VO 2max ) (Marini et al 2007) followed by 4 weeks of detraining to test the hypothesis whether the cessation of aerobic training could reverse training-induced myocardial angiogenesis. The 4-week detraining period was selected on the basis of the time required for an index of training, e.g., the soleus muscle/body weight ratio to return to the baseline value.…”