[Regulation of blood cholesterol, mechanism of hypercholesterolemia]

The concentration of plasma cholesterol essentially reflects the level of low-density lipoproteins (LDL). This LDL level is a function of genetic factors (LDL receptors, apolipoprotein E phenotype) and environmental factors, notably diet. A high plasma level of LDL is one of the major risk factors for coronary disease. A decreased catabolism and/or an increased LDL synthesis may be responsible for abnormally high plasma LDL levels. Among mechanisms of decreased LDL catabolism, deficiency in LDL receptors is the best known and corresponds to familial hypercholesterolaemia. The presence of antibodies to the LDL receptor has been described, and abnormalities in the regulation of LDL receptor number are probably frequent. The latter abnormalities can be amplified by a diet enriched with lipids. A mutation in apolipoprotein B100 decreasing the binding of LDL to its receptor has been shown to be responsible for hypercholesterolaemia. Hypercholesterolaemia by increased LDL synthesis is known, but it may result from primary abnormalities in the regulation of apo-B100 synthesis or be secondary to another lipid modification.