Abstract
The question we are addressing is: “Should the susceptibility of low density lipoproteins (LDL) to oxidation ex vivo be added to the list of risk factors?” My answer will be “No…at least not yet.” First of all, it has yet to be conclusively proved that the oxidative modification hypothesis of atherosclerosis applies to the human disease. Clinical trials have begun and an answer should be available within a few years but at the moment we are not sure. Second, it is not all clear that the efficacy of an antioxidant in protecting LDL against ex vivo oxidation predicts its efficacy in slowing the progression of atherosclerosis, even in animal models of the disease.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Steinberg D, Parthasarathy S, Carew TE, Khoo JC, Witztum JL. Beyond cholesterol. Modifications of low-density lipoprotein that increase its atherogenicity [see comments]. N Engl J Med 1989; 320: 915–24.
Steinberg D. Oxidative modification of LDL and atherogenesis. The 1995 Lewis A. Conner Memorial Lecture. Circulation 1997; 95: 1062–71.
Suzuki H, Kurihara Y, Takeya M, et al. Resistance to atherosclerosis and susceptibility to infection in scavenger receptor knockout mice. Nature 1997; 386: 292–96.
Esterbauer H, Puhl H, Dieber-Rotheneder M, Waeg G, Rabl H. Effect of antioxidants on oxidative modification of LDL. Ann Med 1991; 23: 573–81.
Sasahara M, Raines EW, Chait A, Carew TE, Steinberg D, Wahl PW, Ross R. Inhibition of hypercholesterolemia-induced atherosclerosis in the nonhuman primate by probucol. I. Is the extent of atherosclerosis related to resistance of LDL to oxidation ? J Clin Invest 1994; 94: 155–64.
McPherson R, Hogue M, Milne RW, Tall AR, Marcel YL. Increase in plasma cholesteryl ester transfer protein during probucol treatment. Relation to changes in high density lipoprotein composition. Aterioscler Thromb 1991; 11: 476–81.
Ku G, Thomas CE, Akeson AL, Jackson RL. Induction of interleukin-1- beta expression from human blood monocyte-derived macrophages by 9-hydroxyoctadecadienoic acid. J Biol Chem 1992; 267: 14183–88.
Fruebis J, Steinberg D, Dresel HA, Carew TE. A comparison of the antiatherogenic effects of probucol and of a structural analogue of probucol in low density lipoprotein receptor-deficient rabbits. J Clin Invest 1994; 94: 392–98.
Carew TE, Schwenke DC, Steinberg D. Antiatherogenic effect of probucol unrelated to its hypocholesterolemic effect: evidence that antioxidants in vivo can selectively inhibit low density lipoprotein degradation in macrophage-rich fatty streaks and slow the progression of atherosclerosis in the Watanabe heritable hyperlipidemic rabbit. Proc Natl Acad Sci USA 1987; 84: 7725–29.
Sparrow CP, Doebber TW, Olszewski J, Wu MS, Ventre J, Stevens KA, Chao YS. Low density lipoprotein is protected from oxidation and the progression of atherosclerosis is slowed in cholesterol-fed rabbits by the antioxidant N,N’-diphenyl-phenylenediamine. J Clin Invest 1992; 89: 1885–91.
Fruebis J, Carew TE, Palinski W. Effect of vitamin E on atherogenesis in LDL receptor-deficient rabbits. Atherosclerosis 1995; 117: 217–24.
O’Leary V, Tilling L, Fleetwood G, Stone D, Darley-Usmar V. The resistance of low density lipoprotein to oxidation promoted by copper and its use as an index of antioxidant therapy. Atherosclerosis 1995; 119: 169–79.
Esterbauer H, Dieber-Rotheneder M, Waeg G, Puhl H, Tatzber F. Endogenous antioxidants and lipoprotein oxidation. Biochem Soc Trans 1990; 18: 1059–61.
Prasad K, Kalra J, Lee P. Oxygen free radicals as a mechanism of hypercholesterolemic atherosclerosis: effects of probucol. International J Angio 1994; 3: 100–12.
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1998 Springer Science+Business Media Dordrecht
About this chapter
Cite this chapter
Steinberg, D. (1998). Is “Antioxidant Status” a Risk Factor?. In: Gotto, A.M., Lenfant, C., Paoletti, R., Catapano, A.L., Jackson, A.S. (eds) Multiple Risk Factors in Cardiovascular Disease. Medical Science Symposia Series, vol 12. Springer, Dordrecht. https://doi.org/10.1007/978-94-011-5022-4_18
Download citation
DOI: https://doi.org/10.1007/978-94-011-5022-4_18
Publisher Name: Springer, Dordrecht
Print ISBN: 978-94-010-6108-7
Online ISBN: 978-94-011-5022-4
eBook Packages: Springer Book Archive