Low density lipoprotein receptor regulation and the cellular basis of atherosclerosis: implications for nutritional and pharmacologic treatment of hypercholesterolemia.
Blood levels of lipids and lipoproteins are prominent among the factors identified as contributing to the development of coronary artery disease. Studies have demonstrated that reduction of low density lipoprotein (LDL) levels lowers the risk of coronary events and retards the progression of atherosclerotic lesions. LDL receptors play a central role in the metabolism of LDL: they maintain cellular cholesterol homeostasis by effects on cholesterol synthesis, modulate the plasma level of lipoproteins by clearing LDL from the circulation and deliver cholesterol to the adrenal glands and gonads for steroid hormone synthesis and to the liver for bile acid synthesis. The 2 major strategies that have been developed so far to lower LDL levels involve the use of bile acid-binding resins, which bind cholesterol in the intestinal lumen, thereby leading to a decrease in intracellular cholesterol, which increases the rate of synthesis of LDL receptors and increases the rate of LDL clearance; and, more recently, the use of inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the key enzyme in the biosynthesis of cholesterol. Further studies are required to assess whether HMG-CoA reductase inhibitors, used alone or concomitantly with bile acid-binding resins, are safe and effective for long-term use in patients with elevated LDL levels.
Heber
D
D
Department of Medicine, University of California, Los Angeles School of Medicine.
Koziol
B J
BJ
Henson
L C
LC
D001161:Arteriosclerosis / Q000473:pathology*; D006801:Humans; D006937:Hypercholesterolemia / Q000178:diet therapy / Q000188:drug therapy*; D011973:Receptors, LDL / Q000502:physiology*
D011973:Receptors, LDL