title: Genetic determinants: is there an "atherosclerosis gene"?
abstract: It is now clear that atherosclerotic disease is a chronic inflammatory disease triggered by a sequence of events initiated at sites with turbulent flow under normal conditions such as in the coronary arteries or at bifurcations or where normal laminar flow is replaced by turbulent flow because of vessel pathologies. Normally, laminar flow is protected by generation of NO by endothelial NO synthase (eNOS), which becomes activated via stretch activated channels. When the flow turns turbulent, such protective NO generation ceases, leading to endothelial cell activation and lipid deposition into the extra-cellular space. There, lipoproteins and specifically phospholipids become oxidized by cells of the monocytic-macrophage lineage. Only when the LDL-cholesterol level is high enough lipid peroxidation products are generated in sufficient amounts to perpetuate the disease by generating a feed forward loop of endothelial cell activation leading to an inflammatory response. That inflammatory response might also be added by bacterial or viral infections such as Chlamydia pneumoniae or viruses. The disease then progresses to a chronic inflammatory state, whereby the immune system seems to contribute significantly and markers of chronic inflammation such as fibrinogen, leukocytes, PAI-1 and CRP are found increased.
authors.affiliation: Department of Vascular Biology and Thrombosis Research, Medical University of Vienna, Vienna, Austria.
authors.forename: Gerald W
authors.initials: GW
authors.lastname: Prager
authors.forename: Bernd R
authors.initials: BR
authors.lastname: Binder
mesh_terms: D001161:Arteriosclerosis / Q000097:blood / Q000235:genetics* / Q000473:pathology; D001783:Blood Flow Velocity; D006801:Humans; D007249:Inflammation; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000235:genetics; D052250:Nitric Oxide Synthase Type III; D013314:Stress, Mechanical
chemical_list: D009569:Nitric Oxide; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III