Regulation of low-density lipoprotein receptors: implications for pathogenesis and therapy of hypercholesterolemia and atherosclerosis.
Low-density lipoprotein (LDL) is the most abundant and the most atherogenic class of cholesterol-carrying lipoproteins in human plasma. The level of plasma LDL is regulated by the LDL receptor, a cell surface glycoprotein that removes LDL from plasma by receptor-mediated endocytosis. Defects in the gene encoding the LDL receptor, which occur in patients with familial hypercholesterolemia, elevate the plasma LDL level and produce premature coronary atherosclerosis. The physiologically important LDL receptors are located primarily in the liver, where their number is regulated by the cholesterol content of the hepatocyte. When the cholesterol content of hepatocytes is raised by ingestion of diets high in saturated fat and cholesterol, LDL receptors fall and plasma LDL levels rise. Conversely, maneuvers that lower the cholesterol content of hepatocytes, such as ingestion of drugs that inhibit cholesterol synthesis (mevinolin or compactin) or prevent the reutilization of bile acids (cholestyramine or colestipol), stimulate LDL receptor production and lower plasma LDL levels. The normal process of receptor regulation can therefore be exploited in powerful and novel ways so as to reverse hypercholesterolemia and prevent atherosclerosis.
D000924:Anticholesteremic Agents / Q000627:therapeutic use; D001161:Arteriosclerosis / Q000209:etiology* / Q000628:therapy; D002648:Child; D002784:Cholesterol / Q000097:blood; D006801:Humans; D006937:Hypercholesterolemia / Q000209:etiology* / Q000628:therapy; D006938:Hyperlipoproteinemia Type II / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000097:blood; D008099:Liver / Q000378:metabolism; D008875:Middle Aged; D011973:Receptors, LDL / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D012306:Risk
D000924:Anticholesteremic Agents; D008077:Lipoproteins, LDL; D011973:Receptors, LDL; D002784:Cholesterol