doi: 10.1161/01.RES.0000258450.44413.96
© 2007 American Heart Association, Inc.
Reviews |
Mitochondrial Dysfunction in Atherosclerosis
From the Carolina Cardiovascular Biology Center, Department of Medicine, University of North Carolina, Chapel Hill.
Correspondence to Marschall S. Runge, MD, PhD, Department of Medicine, 3033 Old Clinic Building, University of North Carolina, Chapel Hill, NC 27599-7005. E-mail mrunge{at}med.unc.edu
This Review is part of a thematic series on the Role of Mitochondria in Cardiovascular Diseases, which includes the following articles:
Mitochondrial Dysfunction in Atherosclerosis
Free Radicals, Mitochondria, and Oxidized Lipids: The Emerging Role in Signal Transduction in Vascular Cells
Defective Mitochondrial Biogenesis: A Hallmark of the High Cardiovascular Risk in Metabolic Syndrome?
Mitochondrial Biology and Vascular Biology
Role of Mitochondria in Insulin Resistance
Marshall S. Runge Guest Editor
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 ß-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.
Key Words: oxidative stress • DNA damage • obesity • diabetes • aging
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