Endothelial mitochondria: contributing to vascular function and disease

Abstract

Disturbances in vascular function contribute to the development of several diseases of increasing prevalence and thereby contribute significantly to human mortality and morbidity. Atherosclerosis, diabetes, heart failure, and ischemia with attendant reperfusion injury share many of the same risk factors, among the most important being oxidative stress and alterations in the blood concentrations of compounds that influence oxidative stress, such as oxidized low-density lipoprotein. In this review, we focus on endothelial cells: cells in the frontline against these disturbances. Because ATP supplies in endothelial cells are relatively independent of mitochondrial oxidative pathways, the mitochondria of endothelial cells have been somewhat neglected. However, they are emerging as agents with diverse roles in modulating the dynamics of intracellular calcium and the generation of reactive oxygen species and nitric oxide. The mitochondria may also constitute critical "targets" of oxidative stress, because survival of endothelial cells can be compromised by opening of the mitochondrial permeability transition pore or by mitochondrial pathways of apoptosis. In addition, evidence suggests that endothelial mitochondria may play a "reconnaissance" role. For example, although the exact mechanism remains obscure, endothelial mitochondria may sense levels of oxygen in the blood and relay this information to cardiac myocytes as well as modulating the vasodilatory response mediated by endothelial nitric oxide.