Abstract 205: Aging and Exercise Training Alter Coronary Microvascular Function: Role of the Adiponectin/AMPKinase Axis

Abstract

Our lab has demonstrated age-related coronary microvascular dysfunction can be reversed by aerobic exercise training; however, the mechanisms that underlie age- and exercise training-induced adaptations of the coronary microvasculature remain to be identified. The adipokine, adiponectin, possesses cardioprotective properties, including anti-atherosclerotic and anti-inflammatory effects in the vascular wall, and is known to inhibit vascular smooth muscle (VSM) proliferation in large arteries. Circulating adiponectin declines with age and increases with regular exercise training. Therefore, we hypothesized that alterations in signaling through the adiponectin/AMPKinase axis contribute to age- and exercise training-induced adaptations of the coronary microvasculature, particularly in VSM. Young (4 mos) and old (22 mos) male Fischer 344 rats were randomly assigned to either a sedentary or an exercise training group. Circulating adiponectin levels were measured by ELISA. Coronary arterioles from the left ventricular (LV) free wall were isolated for assessment of contractile function and VSM proliferation, and levels of contractile and proliferative proteins. Circulating adiponectin levels decreased with age and increased after 10 wks of exercise training in both young and old rats. Age impaired contractile responses of coronary arterioles, and increased proliferation of arteriolar VSM. Age reduced levels of AMPKinase and contractile proteins, smooth muscle myosin 1 (SM1) and smooth muscle myosin 2 (SM2), and increased total levels and phosphorylation of ribosomal protein S6 (rpS6), a downstream effector of mammalian target of rapamycin (mTOR). Exercise training reversed age-induced contractile dysfunction and attenuated VSM proliferation in coronary arterioles. Exercise training restored contractile function and reduced proliferation in coronary arterioles from old rats. Exercise training also returned AMPKinase, SM1, rpS6 and phosphorylated rpS6 levels in arterioles of old rats to those found in arterioles of young rats. These data indicate that changes in adiponectin/AMPKinase axis contribute to age- and exercise training-induced alterations of coronary microvascular phenotype and function.