Normal and pathological lipoprotein metabolism.

Lipids are transported in plasma as lipoproteins, and an increase in 1 or more classes of lipoprotein underlies all forms of hyperlipidaemia. Physiological influences on lipoprotein metabolism are age, gender, bodyweight, diet and exercise. Pathological influences include genetic abnormalities, endocrine dysfunction, renal impairment and iatrogenic effects. Three inherited forms of hyperlipidaemia which predispose to atherosclerosis are familial hypercholesterolaemia (FH), type III hyperlipoproteinaemia and familial combined hyperlipidaemia (FCH), each of which has its own distinctive metabolism defect. In FH, deficiency of low density lipoprotein (LDL) receptors results in the accumulation in plasma of LDL-cholesterol because of a reduction in the receptor-mediated component of LDL catabolism. In type III hyperlipoproteinaemia, the presence of an abnormal apo E isoform (apo E2) in remnant particles leads to their accumulation in plasma, through nonrecognition by remnant receptors and a consequent reduced rate of hepatic uptake. In contrast, there is no primary catabolic defect in FCH, in which increased levels of very low density lipoprotein (VLDL) and LDL are largely the result of increased synthesis.