LDL信号通路总结.docVIP

Atherosclerosis, a chronic inflammatory disease of the arterial wall, is the major cause of morbidity and mortality from CVD Cardiovascular Disease in much of the world’s population. The disease involves the formation of Plaques in arterial walls that narrow the arterial passage, restricting blood flow and increasing the risk of occlusion of blood flow by a myocardial infarction. There is now a consensus that Atherosclerosis represents a state of heightened oxidative stress characterized by lipid and protein oxidation in the vascular wall. The Oxidative Modification hypothesis predicts LDL Low-Density Lipoproteins oxidation as an early event in Atherosclerosis, and oxidized LDL as one of the important contributors of Atherogenesis Ref.1, 2 3 . Lipoproteins are water-soluble spherical particles that transport nonpolar lipids. In humans, LDLs are the major Cholesterol transporters and consist of a hydrophobic core containing Cholesteryl ester molecules, Triacylglycerols; and a surface monolayer of polar lipids primarily Phospholipids and ApoB Apolipoprotein-B Ref.4 . LDL is commonly referred to as “Bad Cholesterol” due to its role in promoting Atherosclerosis. Oxidation of LDL in the Artery wall is one of the major physiologically relevant mechanisms for the pathogenesis of Atherosclerosis Ref.5 . LDL in the plasma originates from vLDL very-Low Density Lipoprotein produced by the liver. vLDL is converted to LDL by the action of LPL Lipoprotein Lipase , an enzyme that hydrolyzes triglycerides in vLDL, removing them from the vLDL particle and releasing free fatty acids. The removal of triglycerides from vLDL by LPL leaves a greater proportion of Cholesterol, increasing the density of the particle and changing it to LDL. One of the first steps in the development of Atherosclerosis is the passage of LDL out of the Arterial lumen into the Arterial wall. Plasma LDL is transported across the intact Endothelium and becomes trapped in the ECM Extracellular Matr