The oxidative modification hypothesis of atherosclerosis: does it hold for humans?
This review suggests that oxidation of LDL is an important, if not obligatory, event in atherogenesis. The important clinical corollary is that inhibition of oxidation can inhibit atherosclerosis independent of lowering plasma cholesterol levels. This article surveys the extensive data supporting the presence of oxidized LDL in vivo in animal models; the many studies demonstrating that inhibition of oxidation by pharmacologic and/or genetic manipulations retards atherogenesis; the data in humans that supports a role for oxidation of LDL; and the results of intervention trials with antioxidant vitamins. Limitations of these trials that may have led to inconclusive results to date are discussed, and what this may mean for the oxidation hypothesis. The oxidation hypothesis is still viable, but a great deal needs to be learned in order to design the appropriate clinical trials to properly test the importance of oxidation in the pathogenesis of atherosclerosis in humans.
Witztum
J L
JL
Department of Medicine, Division of Endocrinology and Metabolism, Specialized Center of Research in Molecular Medicine and Atherosclerosis, University of California, San Diego School of Medicine, La Jolla, California, USA. jwitztum@ucsd.edu
Steinberg
D
D
D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology; D001161:Arteriosclerosis / Q000188:drug therapy / Q000378:metabolism*; D002784:Cholesterol / Q000097:blood; D002986:Clinical Trials as Topic; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D012196:Review Literature as Topic
D000975:Antioxidants; D008077:Lipoproteins, LDL; D002784:Cholesterol