Oxidative stress, AGE, and atherosclerosis

摘要: Numerous reports on the molecular mechanism of atherogenesis indicate an increase in oxidative stress, formation advanced glycoxidation end products (AGEs), chronic inflammation, and activated cellular response particularly diabetic patients. To elucidate initiating early accelerating events this review will focus causes induction these stress factors, their interactions, contribution to atherogenesis. Metabolic factors such as elevated free fatty acids, high glucose levels or AGEs induce reactive oxygen species (ROS) vascular cells leading ongoing AGE gene proinflammatory cytokines. Vice versa, numerous cytokines found obesity diabetes may also thus a circulus vitious be initiated accelerated. Increased production ROS, mainly from mitochondria NAD(P)H oxidase, stimulates signaling cascades including protein kinase C mitogen-activated pathway nuclear translocation transcription factor- κ B (NF- B), activator 1, specificity 1. Subsequently, expression genes is rapidly induced, which, turn, act promoting deleterious effects. From animal models accelerated atherosclerosis causal role oxidase AGE/RAGE/NF- axis suggested. Because all involved form highly interwoven network blockade ROS at different sites interrupt vicious cycle. Promising candidate agents are, currently trial. Most important clinical practice, number drugs commonly used treatment diabetes, hypertension, cardiovascular disease, angiotensin-converting enzyme inhibitors, AT 1 receptor blockers, 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors (statins), thiazolidindiones have shown promising ‘preventive' intracellular antioxidant activity addition primary pharmacological actions.