Lipid transport through the plasma: the metabolic basis of hyperlipidaemia

Plasma lipid abnormalities derive their importance from their association with coronary artery disease. Elevated cholesterol levels accentuate risk, and clinical trials have shown that reductions lead to a decline in coronary events. The major plasma lipids, cholesterol and triglyceride, circulate in association with specific proteins as lipid-protein or lipoprotein complexes. The proteins direct and regulate the metabolism of these complexes by interacting with tissue enzymes and receptors. The metabolic fate of circulating triglyceride is governed by the activity of the enzyme lipoprotein lipase, situated in adipose tissue and skeletal muscle. Cellular demand for cholesterol, on the other hand, is met by activation of a specific receptor which mediates the delivery of sterol-rich lipoproteins to lysosomal degradation in liver and peripheral tissues. In order to prevent excess cholesterol accumulation at the periphery, there is a system of reverse cholesterol transport which involves assimilation and trapping of the sterol in the plasma lipoproteins through the action of the enzyme lecithin:cholesterol acyltransferase. Thereafter, the cholesterol is delivered to the liver, the only organ capable of excreting it in significant amounts. Disturbances in these processes may produce gross changes in the plasma lipid profile, clearly recognizable as hyperlipidaemia. However, it is becoming increasingly clear that a number of inherited traits can subtly perturb the lipoprotein spectrum and increase coronary risk even in subjects whose plasma lipoprotein profile would be considered normal.