Role of perivascular adipose tissue on vascular reactive oxygen species in type 2 diabetes: a give-and-take relationship.

Abstract

A major complication of type 2 diabetes (T2D) is atherosclerotic vascular disease, which develops earlier and more rapidly in patients with T2D than in subjects without diabetes (1). One of the characteristic features of T2D is excessive generation of reactive oxygen species (ROS) in the artery wall and the resultant oxidative stress, which contributes to the development of endothelial dysfunction and atherosclerosis (2–5). Moreover, activity of NADPH oxidase, the primary ROS-generating enzyme in vascular cells, has been shown to be increased in T2D (2–5). Notably, behavioral and pharmacological interventions that reduce vascular NADPH oxidase expression and activity demonstrate improvements in endothelial function and reduced atherogenesis (6–8). Furthermore, mice lacking components of the NADPH oxidase subunits are protected against hypertension, and when crossed to the apoE−/− background, they have a marked reduction in vascular ROS production, enhanced nitric oxide bioavailability, and reduced atherosclerotic lesion formation (9,10), thus demonstrating that excessive NADPH oxidase–derived ROS is detrimental to vascular health. Although the recognition that increased vascular NADPH oxidase is an important contributor to vascular complications in T2D, the mechanisms regulating its enzyme activity remain poorly understood. Recent studies implicate adipose tissue adjacent to the artery wall (i.e., perivascular adipose tissue [PVAT]) as playing an important role in the pathogenesis of vascular diseases (11–13). The PVAT serves not …