Lipoproteins and atherosclerosis.
The plasma lipoproteins are the primary means of transport of cholesterol among tissues. In particular, the apo B-containing lipoproteins (VLDL, IDL and LDL) are important for the delivery of cholesterol from the liver to peripheral tissues, while HDL appear to mediate the reverse process of movement of cholesterol from tissues back to the liver. Both of these transport processes are necessary for efficient whole body cholesterol homeostasis, because the liver is the major site of both the production and excretion of cholesterol. However, deviations from a proper balance of transport of cholesterol, either increases in LDL levels or decreases in HDL cholesterol flux, may result in accumulation of cholesterol in extrahepatic tissues. Increased risk of atherosclerosis and CHD may be associated with elevation in the number of LDL particles, increase or decrease in LDL particle size, or changes in the composition of plasma LDL. These modifications of plasma LDL may be brought about following perturbation of one of several aspects of LDL metabolism. These include decreased LDL receptor activity, increased VLDL production and cholesterol enrichment of the liver-derived VLDL. The events in the arterial wall that make some LDL particles apparently atherogenic are not well understood. In the case of nonhuman primates, large-size LDL are associated with an increased risk of CHD. One characteristic of these LDL is that their core lipids are rich in saturated cholesteryl esters and their transition temperatures are frequently above body temperature. The liquid crystalline cholesteryl ester cores of such LDL may modulate the conformation of apo B on the surface and thereby affect the interaction of these LDL with cellular receptors or connective tissue matrix proteoglycans. It is likely, though, that changes in LDL particle number, LDL particle size and LDL particle composition may each contribute to progression of atherosclerosis. The presumed metabolic events that make HDL protective against atherosclerosis have been termed reverse cholesterol transport, and suggest that small HDL that are deficient in free cholesterol acquire this lipid from cell membranes. The HDL cholesterol is esterified by LCAT in the circulation, forming large HDL that can then deliver the cholesteryl ester to the liver by both direct and indirect means. In most circumstances, it is assumed that an increase in plasma HDL cholesterol concentration reflects an increase in the rate at which HDL is removing cholesterol from tissues and, consequently, a decrease in atherosclerosis.(ABSTRACT TRUNCATED AT 400 WORDS)
Babiak
J
J
Rudel
L L
LL
D001055:Apolipoproteins B / Q000502:physiology; D001161:Arteriosclerosis / Q000209:etiology*; D001692:Biological Transport; D002784:Cholesterol / Q000378:metabolism; D003327:Coronary Disease / Q000209:etiology; D004730:Endothelium, Vascular / Q000378:metabolism; D006801:Humans; D008074:Lipoproteins / Q000097:blood / Q000502:physiology*; D008075:Lipoproteins, HDL / Q000097:blood / Q000502:physiology; D008077:Lipoproteins, LDL / Q000097:blood / Q000502:physiology; D008079:Lipoproteins, VLDL / Q000097:blood / Q000502:physiology; D008264:Macrophages / Q000378:metabolism; D008954:Models, Biological; D012307:Risk Factors
D001055:Apolipoproteins B; D008074:Lipoproteins; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D002784:Cholesterol