Madamanchi Nageswara R, Runge Marschall S
Carolina Cardiovascular Biology Center, Department of Medicine, University of North Carolina, Chapel Hill, NC 27599-7005, USA.
Circ Res. 2007 Mar 2;100(4):460-73. doi: 10.1161/01.RES.0000258450.44413.96.
Increased production of reactive oxygen species in mitochondria, accumulation of mitochondrial DNA damage, and progressive respiratory chain dysfunction are associated with atherosclerosis or cardiomyopathy in human investigations and animal models of oxidative stress. Moreover, major precursors of atherosclerosis-hypercholesterolemia, hyperglycemia, hypertriglyceridemia, and even the process of aging-all induce mitochondrial dysfunction. Chronic overproduction of mitochondrial reactive oxygen species leads to destruction of pancreatic beta-cells, increased oxidation of low-density lipoprotein and dysfunction of endothelial cells-factors that promote atherosclerosis. An additional mechanism by which impaired mitochondrial integrity predisposes to clinical manifestations of vascular diseases relates to vascular cell growth. Mitochondrial function is required for normal vascular cell growth and function. Mitochondrial dysfunction can result in apoptosis, favoring plaque rupture. Subclinical episodes of plaque rupture accelerate the progression of hemodynamically significant atherosclerotic lesions. Flow-limiting plaque rupture can result in myocardial infarction, stroke, and ischemic/reperfusion damage. Much of what is known on reactive oxygen species generation and modulation comes from studies in cultured cells and animal models. In this review, we have focused on linking this large body of literature to the clinical syndromes that predispose humans to atherosclerosis and its complications.
在人类研究以及氧化应激动物模型中，线粒体中活性氧生成增加、线粒体DNA损伤积累以及进行性呼吸链功能障碍与动脉粥样硬化或心肌病相关。此外，动脉粥样硬化的主要前驱因素——高胆固醇血症、高血糖、高甘油三酯血症，甚至衰老过程——均会诱发线粒体功能障碍。线粒体活性氧长期过度生成会导致胰岛β细胞破坏、低密度脂蛋白氧化增加以及内皮细胞功能障碍，这些都是促进动脉粥样硬化的因素。线粒体完整性受损导致血管疾病临床表现的另一种机制与血管细胞生长有关。正常的血管细胞生长和功能需要线粒体功能。线粒体功能障碍可导致细胞凋亡，促使斑块破裂。斑块破裂的亚临床发作会加速具有血流动力学意义的动脉粥样硬化病变的进展。限流性斑块破裂可导致心肌梗死、中风和缺血/再灌注损伤。目前关于活性氧生成和调节的许多知识都来自于对培养细胞和动物模型的研究。在本综述中，我们着重将大量此类文献与使人类易患动脉粥样硬化及其并发症的临床综合征联系起来。
