Lipid peroxidation in mouse models of atherosclerosis.
Over the past decade, oxidative modification of low-density lipoprotein (LDL) has been implicated in atherogenesis. This hypothesis has been supported indirectly by a number of in vitro and ex-vivo observations demonstrating the pro-atherogenic properties of oxidized LDL, their occurrence in atherosclerotic lesions and some positive results in animal studies with antioxidants. Only recently, however, have small mammalian models (mouse) of atherosclerosis been created by gene manipulation and widely used by investigators to better elucidate this pathogenetic aspect of such a complex disease. Transgenic animal models combined with the availability of more reliable, specific and sensitive markers of in vivo lipid peroxidation have now provided consistent evidence for a direct and functional role of oxidant stress in atherogenesis. The identification of yet unknown initiating event(s) of in vivo oxidant stress will be the challenge for the future. This should finally provide the basis for the development of most effective antioxidant agents that could modulate atherogenesis.
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Center for Experimental Therapeutics, Department of Pharmacology, University of Pennsylvania, Philadelphia, Pennsylvania, USA. domenico@spirit.gcrc.upenn.edu
D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology; D001161:Arteriosclerosis / Q000378:metabolism*; D004195:Disease Models, Animal; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008955:Models, Cardiovascular; D018384:Oxidative Stress / Q000502:physiology
D000975:Antioxidants