Aging and Vascular Endothelial Dysfunction

Abstract

Older age is a major risk factor for cardiovascular diseases (CVD). This is believed to be attributable in part to the development of vascular endothelial dysfunction, as most commonly demonstrated by impaired endothelium‐dependent dilation (EDD). EDD is reduced in older adults without clinical disease or major risk factors for disease, as well as in animal models resistant to the development of CVD, suggesting a direct effect of aging processes. Several biological and lifestyle factors influence EDD with aging in adult humans including habitual aerobic exercise, body fatness and its distribution, and circulating concentrations of low‐density lipoprotein cholesterol. The integrative physiological mechanisms mediating age‐associated impairments in EDD involve oxidative stress‐associated reductions in nitric oxide bioavailability. The development of vascular inflammation also appears to play a role, likely interacting with oxidative stress via mechanisms that are incompletely understood. Recent work explores the cellular and molecular events that contribute to impaired EDD with aging, including altered posttranslational modification of proteins and signaling. Efforts also are focusing on promising "anti‐aging" pharmacological interventions that may slow or prevent the development of vascular endothelial dysfunction and other clinically important expressions of arterial aging.