Previous exercise training increases levels of PPAR-α in long-term post-myocardial infarction in rats, which is correlated with better inflammatory response

Abstract

OBJECTIVE:Exercise is a protective factor for cardiovascular morbidity and mortality, with unclear mechanisms. Changing the myocardial metabolism causes harmful consequences for heart function and exercise contributes to metabolic adjustment modulation. Peroxisome proliferator-activated receptors (PPARs) are also myocardium metabolism regulators capable of decreasing the inflammatory response. We hypothesized that PPAR-α is involved in the beneficial effects of previous exercise on myocardial infarction (MI) and cardiac function, changing the expression of metabolic and inflammatory response regulators and reducing myocardial apoptosis, which partially explains the better outcome.METHODS AND RESULTS:Exercised rats engaged in swimming sessions for 60 min/day, 5 days/week, for 8 weeks. Both the exercised rats and sedentary rats were randomized to MI surgery and followed for 1 week (EI1 or SI1) or 4 weeks (EI4 or SI4) of healing or to sham groups. Echocardiography was employed to detect left ventricular function and the infarct size. Additionally, the TUNEL technique was used to assess apoptosis and immunohistochemistry was used to quantitatively analyze the PPAR-α, TNF-α and NF-κB antigens in the infarcted and non-infarcted myocardium. MI-related mortality was higher in SI4 than in EI4 (25% vs 12%), without a difference in MI size. SI4 exhibited a lower shortening fraction than EI4 did (24% vs 35%) and a higher apoptosis/area rate (3.97±0.61 vs 1.90±1.82) in infarcted areas (both p=0.001). Immunohistochemistry also revealed higher TNF-α levels in SI1 than in EI1 (9.59 vs 4.09, p<0.001) in infarcted areas. In non-infarcted areas, EI4 showed higher levels of TNF-α and positive correlations between PPAR-α and NF-κB (r=0.75, p=0.02), in contrast to SI4 (r=0.05, p=0.87).CONCLUSION:Previously exercised animals had better long-term ventricular function post-MI, in addition to lower levels of local inflammatory markers and less myocardial apoptosis, which seemed to be related to the presence of PPAR-α.

Untangling the Cooperative Role of Nuclear Receptors in Cardiovascular Physiology and Disease

“…Cardiac expression of PPARα and its FA metabolism target genes decreases with age but increases with exercise [150], which suggests that myocardial PPARα signaling might improve age-dependent FA use. Exercise has also been linked to the protective action of PPARα in MI [151]. These authors found that exercised rats subjected to MI had better Cardiac PPARα is upregulated in a mouse model streptozotocin-induced diabetes [41].…”

Molecular Mechanisms of Cardiac Remodeling and Regeneration in Physical Exercise

“…PPAR are transcription factors mediating the development of cardiac hypertrophy and regulating fatty acid metabolism [132]. Exercise increases PPAR-alpha levels and decreases consequently inflammatory response including TNF-alpha and NF-kB levels [133]. This is important as PPAR-alpha stimulation downregulates inflammatory molecules and decreases infarct size [134].…”

Physical Exercise: A Novel Tool to Protect Mitochondrial Health

“…Both preclinical and clinical studies suggest acute and long-term antiinflammatory effects of exercise by increasing anti-inflammatory cytokines and reducing pro-inflammatory mediators (IL-6 and TNFalpha) in different tissues (Metsios et al, 2020). The antiinflammatory action is due to increased transcription factor PPAR alpha and the reduction of NFkappaB levels (Santos et al, 2016). Moreover, PA improves endothelial function by reducing reactive oxygen species production and increasing nitric oxide bioavailability (Di Francescomarino et al, 2009;Skrypnik et al, 2014).…”