Antioxidants in atherosclerosis

Steinberg D. 2000. Is there a potential therapeutic role for vitamin E or other antioxidants in atherosclerosis Curr. Opin. Lipidol. 11 603-7... 

Steinberg, D. (1995). Role of oxidized LDL and antioxidants in atherosclerosis, in Biotechnology in Heart Disease and Cancer, Longenecker, J.B., Kritchevsky, D., and Drezner, M.K., Eds., Plenum Press, New York and London, 1. 

Probucol. Probucol is an antioxidant that is effective in lowering LDL cholesterol. Whereas probucol was known to lower cholesterol after relatively simple clinical trials (160), its mechanism of action as an antioxidant in the treatment of atherosclerosis is quite novel. Probucol has been shown to have the abiUty to produce regression of atherosclerotic lesions in animal models (161). Probucol therefore represents a novel class of pharmaceutical agent for the treatment of atherosclerosis. This effect occurs mechanistically, in part, by preventing oxidation of LDL, a necessary step in foam cell formation. This antioxidant activity has been shown in laboratory experiments and its activity in lowering LDL cholesterol in human studies is well documented (162). 

CHOPRA M, MCLOONE u L, o neill m, WILLIAMS N and THURNHAM DI (1996) Fruit and vegetable supplementation - effect on ex vivo LDL oxidation in hiunans , in Kumpulainen, J T and Saonen, J T (eds), Natural Antioxidants and Food Quality in Atherosclerosis and Cancer Prevention, Cambridge, Royal Society of Chemistry, 150-55. 

LDL when oxidized is recognized to play a crucial role in the development of atherosclerosis. It was thought that flavonoids could also protect LDL against oxidation, especially by limiting the degradation of vitamin E, the main antioxidant in LDL. Other beneficial effects of flavonoids have been reported inhibition of platelet... 

In atherosclerosis and other heart diseases, the role of carotenoids as antioxidants is probable, but for these types of diseases and also for other degenerative diseases such as cancers, non-antioxidant activities constitute other possible prevention mechanisms. These activities are, for example, stimulation of gap junction communications between cells, and the induction of detoxifying enzymes. The... 

Carew, T.E., Schwenke, D.C. and Steinberg, O. (1987). Antiatherogenic effect of probucol unrelated to its hyper-cholesterolaemic effect evidence that antioxidants in vim can selectively inhibit low density lipoprotein degradation in macroph -rich fatty streaks slowing the progression of atherosclerosis in the WHHL rabbit. Proc. Natl Acad. Sci. USA 84, 7725-7729. 

Depletion of the antioxidant capacity of LDL is an early event in the oxidation process. The main antioxidant in LDL is a-tocopherol, with smaller quantities of 0-carotene and 7-tocopherol also present. The importance of antioxidants in inhibiting the oxidative modification of LDL is su ested by human and animal studies on the prevention of atherosclerosis. Preliminary reports... 

There have been more than 20 studies relating to the prevention of atherosclerosis by antioxidants. In vitro, several studies have shown that antioxidant treatment (e.g. vitamin E) inhibits both oxidation and the formation of cytotoxic LDL (Steinbrecher etal., 1984 Par-thasarathy etal., 1986 Esterbauer etal., 1987). In vivo, vitamin E supplementation prevents LDL oxidation in... 

Murr C, Winklhofer-Roob BM, Schroecksnadel K, Maritschnegg M, Mangge H, Bohm BO, Winkelmann BR, Marz M and Fuchs D. 2009. Inverse association between serum concentrations of neopterin and antioxidants in patients with and without angiographic coronary artery disease. Atherosclerosis. In press. 

Chelators of transition metals, mainly iron and copper, are usually considered as antioxidants because of their ability to inhibit free radical-mediated damaging processes. Actually, the so-called chelating therapy has been in the use probably even earlier than antioxidant therapy because it is an obvious pathway to treat the development of pathologies depending on metal overload (such as calcium overload in atherosclerosis or iron overload in thalassemia) with compounds capable of removing metals from an organism. Understanding of chelators as antioxidants came later when much attention was drawn to the possibility of in vivo hydroxyl radical formation via the Fenton reaction ... 

Aviram, M., Antioxidants in restenosis and atherosclerosis, Curr. Interven. Cardiol. Rep., 1, 66,1999. 

Aviram, M., Interaction of oxidized low density lipoprotein with macrophages in atherosclerosis and the anti-atherogenicity of antioxidants, Eur. J. Clin. Chem. Clin. Biochem., 34, 599, 1996. 

However, none of compounds A-E was found to be able to inhibit squalene epoxidase. On the contrary, compound G has been shown to be an excellent antioxidant in this reaction. It presents a potential cure for atherosclerosis and other diseases related to oxidation.497... 

Nevertheless, the summary of the proceedings [137] of a National Heart, Lung, and Blood Institute workshop September 5-6, 1991, Bethesda, MD, entitled Antioxidants in the prevention of human atherosclerosis will serve as a conclusion "More Basic Research is needed on the mechanisms involved in the oxidative modification of LDL and on the ways in which various antioxidants influence it and More animal studies are needed to establish firmly that protection of LDL against oxidative modification does influence the progression of lesions . 

The oxidative modification of LDL has been implicated in atherosclerosis. This disease may be regarded as a chronic inflammatory condition, and here we discuss how oxidatively modified LDL (oLDL) may play a role not only in atherosclerosis but also in other chronic inflammatory diseases such as RA. LDL (Mr = 2.5 x 106) is one of the major plasma carriers of lipids, as well as the antioxidants vitamin E and (3-carotene. Because of its high content of unsaturated fatty acids, LDL is uniquely sensitive to lipid peroxidation [ 117]. 

Katsiki, N. Manes, C. 2009. Is there a role for supplemented antioxidants in the prevention of atherosclerosis Clin. Nutr. 28 3-9. 

Mensink, R.R et al.. Effects of plant stanol esters supplied in low-fat yogurt on serum lipids and lipoproteins, noncholesterol sterols and fat soluble antioxidant concentrations, Atherosclerosis, 160, 205, 2002. 

H. Est auer, R. Schmidt and M. Hayn, Relationships Among Oxidation of Low-Density Lipoprotein, Antioxidant Protection, and Atherosclerosis. In H. Sies (ed.) Advances in Pharmacology Antioxidants in Disease Mechanisms and Therapy. Academic Press Inc., London, 1997 vol. 38, pp.425-455. 

Interventions that block oxidative modification of LDL are currently under intensive study [1,3-5,10]. If oxidative modification of LDL results in enhanced uptake by macrophages, use of an appropriate antioxidant should protect LDL from oxidation, decrease the rate of LDL uptake by macrophage foam cells and slow the development of fatty streaks in the arterial wall. The role of antioxidants in preventing oxidative modification of LDL has been evaluated in a number of studies [1,5,8,10]. In our investigation we studied the influence of the vitamin E reach diet on the copper-mediated oxidizability of plasma LDL from patients with atherosclerosis. So far as LDL is the main transport form of natural antioxidant a-tocopherol we were surprised to find that during 3-months vitamin E supplementation in the daily dose 400 mg the oxidation resistance of LDL did not increase (Figure 14). 

AbdAllaJ,ElFaramawyY, QuittererU (2013) Microarray gene expression profiling reveals antioxidant-like effects of angiotensin II inhibition in atherosclerosis. Front Physiol 4 148... 

Kumpulainen, J.T. and Salonen, J.T. 1996. Natural Antioxidants and Food Quality in Atherosclerosis and Cancer Prevention . The Royal Society of Chemistry, Cambridge. 

---