Mitochondrial dysfunction and mitochondrial DNA mutations in atherosclerotic complications in diabetes  

作　　者：Dimitry A Chistiakov Igor A Sobenin Yuri V Bobryshev Alexander N Orekhov 

机构地区：[1]Department of Medical Nanobiotechnology,Pirogov Russian State Medical University,117997 Moscow,Russia [2]Institute for Atherosclerosis Research,Skolkovo Innovative Centre,121609 Moscow,Russia [3]Institute of General Pathology and Pathophysiology,Russian Academy of Medical Sciences,125315 Moscow,Russia [4]Russian Cardiology Research and Production Complex,121552 Moscow,Russia [5]Faculty of Medicine,School of Medical Sciences,University of New South Wales,NSW 2052,Sydney,Australia

出　　处：《World Journal of Cardiology》2012年第5期148-156,共9页世界心脏病学杂志（英文版）（电子版）

基　　金：Supported by The Russian Ministry of Science and Education

摘　　要：Mitochondrial DNA(mtDNA) is particularly prone to oxidation due to the lack of histones and a deficient mismatch repair system.This explains an increased mutation rate of mtDNA that results in heteroplasmy,e.g.,the coexistence of the mutant and wild-type mtDNA molecules within the same mitochondrion.In diabetes mellitus,glycotoxicity,advanced oxidative stress,collagen cross-linking,and accumulation of lipid peroxides in foam macrophage cells and arterial wall cells may significantly decrease the mutation threshold required for mitochondrial dysfunction,which in turn further contributes to the oxidative damage of the diabetic vascular wall,endothelial dysfunc-tion,and atherosclerosis.Mitochondrial DNA (mtDNA) is particularly prone to oxidation due to the lack of histones and a deficient mismatch repair system. This explains an increased mutation rate of mtDNA that results in heteroplasmy, e.g., the coexistence of the mutant and wild-type mtDNA molecules within the same mitochondrion. In diabetes mellitus, glycotoxicity, advanced oxidative stress, collagen cross-linking, and accumulation of lipid peroxides in foam macrophage cells and arterial wall cells may significantly decrease the mutation threshold required for mitochondrial dysfunction, which in turn further contributes to the oxidative damage of the diabetic vascular wall, endothelial dysfunction, and atherosclerosis.

关 键 词：MITOCHONDRIAL DNA Mutation HETEROPLASMY ATHEROSCLEROSIS DIABETES Oxidative stress ULTRASTRUCTURE 

分 类 号：R587.1[医药卫生—内分泌] R543.5[医药卫生—内科学]