Mitochondrial dysfunction and mitochondrial DNA mutations in atherosclerotic complications in diabetes
Mitochondrial dysfunction and mitochondrial DNA mutations in atherosclerotic complications in diabetes
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DOI：
10.4330/wjc.v4.i5.148
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发表时间：
2012-05-26
影响因子：
1.9
通讯作者：
Orekhov, Alexander N.
中科院分区：
文献类型：
--
作者：
Chistiakov, Dimitry A.;Sobenin, Igor A.;Orekhov, Alexander N.
线粒体DNA（mtDNA）由于缺乏组蛋白和缺陷的错配修复系统而特别容易氧化。这解释了mtDNA突变率的增加导致异质性，例如，突变型和野生型mtDNA分子在同一个线粒体内共存。在糖尿病中，糖毒性、晚期氧化应激、胶原交联和泡沫巨噬细胞和动脉壁细胞中脂质过氧化物的积累可显著降低线粒体功能障碍所需的突变阈值，这进而进一步促成糖尿病血管壁的氧化损伤、内皮功能障碍和动脉粥样硬化。(C)2012年百世登。All rights reserved.
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. (C) 2012 Baishideng. All rights reserved.