[The role of lipids in atherogenesis].
The lipoproteins derived from cholesterol are the key to understanding atherogenesis. The main source of lipids for macrophages presented in the subendothelial space are lipoproteins undergoing oxidative modification or aggregation. Lipoproteins internalized in macrophages via endocytosis or phagocytosis are delivered to peripheral endosomes or lysosomes, where they are hydrolyzed. Large amounts of cholesteryl esters bound to cytoplasmic membranes are permanently affected by neutral hydrolase and repeated re-esterification by ACAT. Liberated free cholesterol is provided to the plasma membrane and other intracellulare structures, probably by vesicular transport. This transport is probably partially mediated by npc1 and npc2 (HE1) proteins, as well as lysobiphosphatidic acid. If some cholesterol acceptors, for example HDL particles, are available, some of the cholesterol can leave the cell, enter the circulation, and be transported to the liver in a process of reverse cholesterol transport. Modification of the lipid droplets fluidity by lipid composition is an important factor in susceptibility to this cholesterol efflux. The free cholesterol, especially crystalline, induces apoptosis. Finally, foam cells die and cellular cholesterol esters and free cholesterol are released into the lesion. This represents lipid or necrotic core formation in advanced atheromata. In this paper the role of oxysterols, triglycerides, fatty acids, and phospholips in atherogenesis are also described.
Skoczyńska
Anna
A
Katedra i Klinika Chorób Wewnetrznych, Zawodowych i Nadciśnienia Tetniczego Akademii Medycznej we Wrocławiu. annaskoc@ak.am.wroc.pl
D000818:Animals; D050197:Atherosclerosis / Q000503:physiopathology*; D002784:Cholesterol / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D010084:Oxidation-Reduction; D010743:Phospholipids / Q000096:biosynthesis; D014280:Triglycerides / Q000378:metabolism
D008077:Lipoproteins, LDL; D010743:Phospholipids; D014280:Triglycerides; D002784:Cholesterol