Exercise training regulates autophagy in aorta

Objective Atherosclerosis, an inflammatory vascular disease in large‐ and medium sized arteries, is characterized by the formation of atherosclerotic plaques. It has been demonstrated that exercise training decreases atherosclerotic plaque formation and reduces the levels of circulating pro‐inflammatory cytokines; but it is unknown how reduction of inflammatory cytokines by exercise contribute to the inhibition of atherosclerosis. Autophagy is a reparative and life‐sustaining process by which cytoplasmic components are sequestered in double‐membrane vesicles and degraded upon fusion with lysosomal compartments. Recent studies indicate that autophagy is stimulated in advanced atherosclerotic plaques by oxidized lipids, metabolic stress and inflammation. However, it is not clear whether exercise training modulates autophagy in arteries. Methods Here, we examined whether exercise training regulates autophagy in the aorta of male C57BL/6J and apolipoprotein E deficient mice. C57BL/6J were fed normal chow. Apolipoprotein E deficient mice were fed 45% high‐fat diet to induce atherosclerosis. Mice were randomly assigned into exercise training groups and sedentary group. Exercise training mice were individually housed in cages equipped with a running wheel for 16 weeks. Heart, aorta, blood and plantaris muscle were harvested at 24 hours after the last bout of exercise. To quantify atherosclerotic lesions, we stained aortic root sections with Oil Red O and hematoxylin‐eosin. Autophagy protein expression in aorta was analyzed by western blot. Serum inflammatory cytokines were measured by Proteome Profile Antibody Arrays. Results Voluntary running in C57BL/6J mice resulted in reduced autophagy flux (i.e., a combination of decreased LC3‐II/LC3‐I ratio, LC3‐II levels and tend to increase p62/sequestosome 1 protein content) in aorta. Exercise training significantly reduced atherosclerotic plaque area at the aortic root in apolipoprotein E deficient mice. Autophagy flux in the aorta was significantly lower in exercise trained apolipoprotein E deficient mice when compared to sedentary mice. Serum inflammatory cytokines in exercise trained apolipoprotein E deficient mice were significantly lower than sedentary mice. Conclusions These results suggest that the regular exercise‐mediated reduction of inflammatory cytokines is also associated with a potential decrease in autophagy levels in aorta, which may contribute to the attenuation of atherosclerosis. Support or Funding Information Grant‐in‐Aid for Challenging Exploratory Research (26560404) to Okutsu M.