Role of VDAC in coronary endothelial cell dysfunction in type 1 diabetic mice

Endothelial dysfunction is a common feature of diabetic vascular complications. Rarefaction of capillaries in the heart, as a result of coronary endothelial dysfunction, represents one of the most critical mechanisms involved in cardiac ischemia. The voltage‐dependent anion channel (VDAC) plays an important role in the regulation of mitochondrial metabolic function and mitochondria‐mediated apoptosis. The objective of this study is to examine the role of VDAC in coronary endothelial dysfunction in diabetes. Endothelial cells (ECs) were more apoptotic in the left ventricle of diabetic mice and hyperglycemia induced significant increase in mitochondrial Ca 2+ concentration and VDAC protein levels in coronary ECs. The expression of VDAC‐shRNA in diabetic MCECs not only decreased the mitochondrial Ca 2+ concentration, but also attenuated mitochondrial superoxide anion (O 2 − ) production and the activity of the mitochondrial permeability transition pore opening (an indirect indicator of cell apoptosis) toward control levels. These data suggest that the increased VDAC protein expression in diabetic MCECs leads to the activation of pro‐apoptotic cascade and normalizing VDAC protein level may help to decrease endothelial cell apoptosis, increase capillary density in the heart, and subsequently decrease the incidence of cardiac ischemia in diabetes. This research was supported by grant HL115578.