Free radicals in atherosclerosis

Hunt, J. (1994). Glucose chemistry and atherosclerosis in diabetes mellitus. In Free Radicals in the Environment, Medicine and Toxicology. Current Aspects and Current Highlights (eds. H. Nohl, H. Esterbauer and C. Rice-Evans) pp. 137-162, Richelieu Press, London. 

The Vascular Lesion in Diabetes 183 5.3 Free Radicals and Atherosclerosis 191... 

Thomas SR and Stocker R (2000) Molecular action of vitamin E in lipoprotein oxidation implications for atherosclerosis. Free Radicals in Biology and Medicine 28,1795-1805. 

Atherosclerosis, cancer and degenerative brain diseases may result from specific processes in an organ or a cell system and at the same time may be the result of the universal aging process. Damage to DNA by radicals may be a significant contributor to the age-dependent development of cancer (Halliwell, 1994). Diseases associated with oxidative stress, free radicals and metabolites generating free radicals in the body are listed in Table 3.7 (Stahelin, 1999). It is not yet clear, however, whether the oxidative stress is the primary cause of the diseases or whether formation of radicals is a secondary effect of tissue damage caused by the disease. 

Rikitake Y, Kawashima S, Takeshita S etal. (2001) Anti-oxi-dative properties of fluvastatin, an HMG-CoA reductase inhibitor, contribute to prevention of atherosclerosis in cholesterol-fed rabbits. Atherosclerosis 154 87-96 Riley PA (1994) Free radicals in biology oxidative stress and the effects of ionizing radiation. Int J Radiat Biol 65 27-33... 

Hydroperoxidases protect the body against harmful peroxides. Accumulation of peroxides can lead to generation of free radicals, which in turn can dismpt membranes and perhaps cause cancer and atherosclerosis. (See Chapters 14 and 45.)... 

BERLINER J A and HEINECKE J w (1996) The role of oxidized lipoproteins in atherosclerosis Free Radical Biology and Medicine 20, 707-27. 

STEINBRECHER u p, ZHANG H and LOUGHEED M L (1990) Role of oxidatively modified LDL in atherosclerosis Free Radical Biology and Medicine 9, 155-68. 

Convincing evidence indicates that ROS generated both endogenously and also in response to diet and lifestyle factors may play a significant role in the etiology of atherosclerosis and CHD. Indeed, free radicals are responsible for LDL oxidation, which is involved in the initiation and promotion of atherosclerosis. Thus, protection from LDL oxidation by antioxidants such as carotenoids may lead to protection against human CHD. 

Iron-stimulated free radical-mediated processes are not limited to the promotion of peroxidative reactions. For example, Pratico et al. [188] demonstrated that erythrocytes are able to modulate platelet reactivity in response to collagen via the release of free iron, which supposedly catalyzes hydroxyl radical formation by the Fenton reaction. This process resulted in an irreversible blood aggregation and could be relevant to the stimulation by iron overload of atherosclerosis and coronary artery disease. 

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 ... 

It has been found that the 3-hydroxy-3-methylglutaryl-CoA (HMG CoA) inhibitors statins (atorvastatin, pravastatin, and cerivastatin), widely prescribed cholesterol-lowering agents, are able to inhibit phorbol ester-stimulated superoxide formation in endothelial-intact segments of the rat aorta [64] and suppress angiotensin II-mediated free radical production [65]. Delbose et al. [66] found that statins inhibited NADPH oxidase-catalyzed PMA-induced superoxide production by monocytes. It was suggested that statins can prevent or limit the involvement of superoxide in the development of atherosclerosis. It is important that statin... 

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