Exercise Training Attenuates Vascular Smooth Muscle Remodeling of Coronary Microvasculature in Aged Heart

Late life exercise training reverses age‐induced coronary microvascular dysfunction; however, the cellular mechanisms that underlie this reversal have not been identified. We tested the hypothesis that exercise training attenuates age‐induced vascular smooth muscle remodeling and proliferation, thus contributing to an improvement of microvascular function in coronary arterioles from old rats. Young and old Fischer 344 rats underwent daily exercise training (15 m/min, 15° incline, 1 hr/d, 5 d/wk for 10 wks) or served as sedentary controls. At the end of training, coronary arterioles were isolated, pressurized and fixed, and subsequently cryosectioned to assess vascular smooth muscle cell number and size, and vascular smooth muscle proliferation via immunohistochemistry. Serum samples were obtained to measure circulating adiponectin, an adipokine that promotes vascular smooth muscle differentiation. Immunoblot analysis was performed on pooled arteriolar samples to assess arteriolar protein levels of adenosine monophosphate‐activated kinase (AMPK), a downstream signaling protein of adiponectin receptors, smooth muscle myosin heavy chain isoform I (SMM I), and the synthetic protein, ribosomal protein s6 (rpS6). Aging increased vascular smooth muscle cell size and correspondingly reduced the number of vascular smooth muscle cells per cross‐sectional unit of vascular smooth muscle. Aging increased vascular smooth muscle cell proliferation. Aging decreased circulating adiponectin and reduced the levels of AMPK and SMM I in coronary arterioles; whereas the level of rpS6 increased in arterioles from old rats. After exercise training, the age‐related difference in the number and size of smooth muscle cells was no longer detectable. Exercise training also decreased vascular smooth muscle cell proliferation in arterioles from old rats, and increased circulating adiponectin in both young and old rats. Exercise training increased the level of SMM I in arterioles from old rats. Age‐related differences in the arteriolar levels of AMPK and rpS6 were no longer detectable in coronary arterioles after exercise training. These results indicate that exercise training‐induced reversal of coronary microvascular dysfunction in the aged heart is linked to attenuation of smooth muscle proliferation and hypertrophy. Furthermore, the restorative effect of exercise training on coronary microvascular function may result from adiponectin‐driven changes in the vascular smooth muscle cell phenotype characterized by increased expression of contractile proteins and reduced expression of synthetic proteins. Support or Funding Information NIH R01 HL077224 and NIH R01 HL90937