Atherosclerosis as disease of redox-sensitive genes.
Accumulating evidence provides a compelling case that one of the major pathophysiologic mechanisms involved in the pathogenesis of atherosclerosis is enhanced oxidative stress and that the most important manifestation of this altered redox state is the modulation of a set(s) of proinflammatory genes that are regulated directly or indirectly by reactive oxygen species. Viewed in this perspective the oxidation of LDL is but one important consequence of a generalized metabolic abnormality of the arterial wall in atherosclerosis rather than being the core pathophysiological feature. The fact that hypercholesterolemia, hypertension, and AGEs related to diabetes mellitus all activate similar redox-sensitive proinflammatory genes associated with the pathogenesis of atherosclerosis provides the potential for the development of unifying concepts concerning the etiology of the disease. These concepts also provide additional evidence that antioxidants may be potentially attractive therapeutic agents.
Alexander
R W
RW
Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001158:Arteries / Q000473:pathology; D001161:Arteriosclerosis / Q000209:etiology / Q000235:genetics* / Q000378:metabolism*; D002448:Cell Adhesion; D048909:Diabetes Complications; D004730:Endothelium, Vascular / Q000473:pathology; D006801:Humans; D006973:Hypertension / Q000378:metabolism; D007249:Inflammation / Q000209:etiology / Q000473:pathology; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D019010:Vascular Cell Adhesion Molecule-1 / Q000502:physiology
D000975:Antioxidants; D019010:Vascular Cell Adhesion Molecule-1