糖尿病中线粒体功能与内皮细胞的关系

J. Smooth Muscle Res. (2012) 48 (1): 1–26Correspondence to: Ayako Makino, Ph.D., Section of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Illinois at Chicago, 1819 West Polk Street, M/C 640, Chicago, Illinois 60612, USA Phone: +1312-355-1018 Fax: +1312-413-0437 e-mail: aymakino@uic.edu ©2012 The Japan Society of Smooth Muscle Research 1Invited Review for the 2011 Hirosi Kuriyama Award

Mitochondrial function in vascular endothelial cell

in diabetes

Meenal P angare and Ayako M akino

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 +, Ca 2+). Endothelial mitochondria are mainly responsible for generation of reactive oxy-

gen species (ROS) and maintaining the Ca 2+ 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 production and Ca 2+ overload in mitochondria not

only cause the maladaptive effect on the endothelial function, but also are potentially detrimen-

tal to cell survival. In this article, we review the physiological and pathophysiological role of

mitochondria in endothelial function with special focus on diabetes.

Key words: fission and fusion, biogenesis, mitophagy, apoptosis, complications

Introduction

Diabetes is a metabolic disorder characterized by glucose intolerance and hyperglycemia due to deficiency of insulin and/or loss of effectiveness to insulin action. There are two main types of diabe -tes: Type-1 diabetes and Type-2 diabetes. Type-1 diabetes mellitus is mainly caused by autoimmune destruction of the beta cells in the islets of pancreas, where insulin is secreted upon glucose absorption.

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