Radical Roles for RAGE in the Pathogenesis of Oxidative Stress in Cardiovascular Diseases and Beyond

摘要: Oxidative stress is a central mechanism by which the receptor for advanced glycation endproducts (RAGE) mediates its pathological effects. Multiple experimental inquiries in RAGE-expressing cultured cells have demonstrated that ligand-RAGE interaction generation of reactive oxygen species (ROS) and consequent downstream signal transduction regulation gene expression. The primary RAGE generates oxidative via activation NADPH oxidase; amplification mechanisms mitochondria may further drive ROS production. Recent studies indicating cytoplasmic domain binds to formin mDia1 provide support critical roles this pathway stress; was required rac1 oxidase murine aortic smooth muscle treated with ligand S100B. In vivo, multiple distinct disease models animals, action modulates cellular/tissue fate range disorders, such as myocardial ischemia, atherosclerosis, aneurysm formation. Blockade or genetic deletion shown be protective these settings. Indeed, beyond cardiovascular disease, evidence accruing human subjects linking levels ligands soluble disorders doxorubicin toxicity, acetaminophen neurodegeneration, hyperlipidemia, diabetes, preeclampsia, rheumatoid arthritis pulmonary fibrosis. key strategy prevention deleterious consequences stress, particularly chronic disease.