The oxidant stress hypothesis of atherogenesis.
Atherosclerosis is the commonest lesion of blood vessels and is responsible for life-threatening events such as myocardial infarction and stroke. In the last two decades a series of excellent studies unraveled biochemical mechanisms that provided the background for a theory of atherogenesis. This theory is centered on foam cells and on free radical-mediated modification of low density lipoprotein (LDL). Foam cells are the main cell type of atherosclerotic lesions and originate from monocytes migrated from blood and from smooth muscle cells of the arterial wall. Foam cells are engulfed of lipids taken from LDL. Paradoxically, accumulation of LDL in developing foam cells does not occur via the classic LDL receptor. Incubation of macrophages with even very high concentrations of LDL does not appreciably increase cholesterol content. Chemically modified LDL easily enter the cells of atherosclerotic plaque via an unregulated receptor, the scavenger receptor. The most studied chemical modification of LDL is that induced by free radicals.
Iuliano
L
L
Department of Internal Medicine, Institute of Clinical Medicine I, University La Sapienza, Rome, Italy. luigi.iuliano@uniroma1.it
D001161:Arteriosclerosis / Q000209:etiology*; D005487:Foam Cells; D005609:Free Radicals; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008565:Membrane Proteins; D008954:Models, Biological; D018384:Oxidative Stress; D011971:Receptors, Immunologic / Q000378:metabolism; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B
D005609:Free Radicals; D008077:Lipoproteins, LDL; D008565:Membrane Proteins; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B