Is atherosclerosis a mitochondrial disorder?
There is increasing evidence that damage to the vascular environment from oxidative stress plays a major role in the pathogenesis of atherosclerosis in addition to classical risk factors, such as age, arterial hypertension, diabetes, dyslipidemia, smoking, vascular wall inflammation, or genetic predisposition. Oxidative stress results from the endogenous or exogenous generation of reactive oxidative or nitrogen species, generated by the respiratory chain or enzymatic sources. Oxidative stress results in lipid peroxidation, damage of mitochondrial components including mitochondrial DNA, mitochondrial dysfunction, damage of endothelial cells, vascular smooth muscle cells, and erythrocytes, and lastly apoptosis via either the receptor-mediated pathway or the mitochondria-mediated pathway and activation of the caspase cascade. Though re-balancing of the redox homeostasis by various agents is clinically hardly effective, various trials with experimental agents are promising in this respect. Overall, atherosclerosis appears to be the endpoint of various different pathogenetic mechanisms, of which oxidative stress and disturbed mitochondrial metabolism and function are key factors.
Finsterer
J
J
Krankenanstalt Rudolfstiftung, Vienna, Austria. fifigs1@yahoo.de
D050197:Atherosclerosis / Q000175:diagnosis* / Q000503:physiopathology; D020169:Caspases / Q000502:physiology; D004249:DNA Damage; D004272:DNA, Mitochondrial; D004579:Electron Transport / Q000502:physiology; D004730:Endothelium, Vascular / Q000503:physiopathology; D006801:Humans; D015227:Lipid Peroxidation / Q000502:physiology; D028361:Mitochondrial Diseases / Q000175:diagnosis* / Q000503:physiopathology; D009131:Muscle, Smooth, Vascular / Q000503:physiopathology; D010085:Oxidative Phosphorylation; D018384:Oxidative Stress / Q000502:physiology; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
D004272:DNA, Mitochondrial; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D020169:Caspases