The oxidative modification hypothesis of atherosclerosis: Does it hold forhumans?

This review suggests that oxidation of LDL is an important, if not obligato ry, event in atherogenesis. The important clinical corollary is that inhibi tion of oxidation can inhibit atherosclerosis independent of lowering plasm a cholesterol levels. This article surveys the extensive data supporting th e presence of oxidized LDL in vivo in animal models; the many studies demon strating that inhibition of oxidation by pharmacologic and/or genetic manip ulations 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 res ults to date are discussed, and what this may mean for the oxidation hypoth esis. The oxidation hypothesis is still viable, but a great deal needs to b e learned in order to design the appropriate clinical trials to properly te st the importance of oxidation in the pathogenesis of atherosclerosis in hu mans. (C) 2001, Elsevier Science Inc.