Oxidized Phospholipids as Mediators of Vascular Disease

摘要: Atherosclerosis has been thought to be an inevitable consequence of aging, but progress in understanding the molecular and pathological basis this vascular disease through work Brown Goldstein (1) made it clear that need not case. Specific risk factors for exist, these elucidate general mechanisms underlying disease. For example, failure adequately remove plasma cholesterol form low-density lipoprotein (LDL) from bloodstream, due mutations LDL receptor, leads high concentration is sufficient cause Other (2) demonstrated underwent oxidative modification generate particles were more effective causing effects. Elevated levels promoted pathologic change. Ross proposed a “response-to-injury” model atherosclerosis (3), where damage vessel wall initiated A refined version recognizes early steps atherogenesis necessarily by cytotoxicity oxidized LDL, rather activation inflammatory response tissue. Oxidation inappropriately stimulates normal endothelial cells leukocytes. Activation normally tightly regulated program, which themselves are well regulated, (i.e. oxidation uncontrolled chemical reactions) chronic, unregulated inflammation wall. Such chronic process remodels wall, drives plaque formation, destabilizes structures, all key events atherosclerosis.