糖尿病中线粒体功能与内皮细胞的关系.pdf

J. Smooth Muscle Res. (2012) 48 (1): 1–26 1 Invited Review for the 2011 Hirosi Kuriyama Award Mitochondrial function in vascular endothelial cell in diabetes Meenal Pangare and Ayako Makino University of Illinois at Chicago, USA Received December 24, 2011; Accepted January 13, 2012 Abstract Micro- and macrovascular complications are commonly seen in diabetic patients and en- dothelial dysfunction contributes to the development and progression of the complications. Abnormal functions in endothelial cells lead to the increase in vascular tension and atheroscle- rosis, followed by systemic hypertension as well as increased incidence of ischemia and stroke in diabetic patients. Mitochondria are organelles serving as a source of energy production and as regulators of cell survival (e.g., apoptosis and cell development) and ion homeostasis (e.g., H+, Ca2+). Endothelial mitochondria are mainly responsible for generation of reactive oxy- gen species (ROS) and maintaining the Ca2+ concentration in the cytosol. There is increasing evidence that mitochondrial morphological and functional changes are implicated in vascular endothelial dysfunction. Enhanced mitochondrial fission and/or attenuated fusion lead to mi- tochondrial fragmentation and disrupt the endothelial physiological function. Abnormal mito- chondrial biogenesis and disturbance of mitochondrial autophagy increase the accumulation of damaged mitochondria, such as irreversibly depolarized or leaky mitochondria, and facilitate cell death. Augmented mitochondrial ROS producti