Modified LDL in humans

Epidemiological experimental and clinical data support a primary atherogenic role for plasma low density lipoproteins (LDL) (1). The mechanism by which LDL are mostly cleared form the blood circulation is the LDL receptor pathway which is normally regulated by a feedbak mechanism thus preventing the accumulation of cholesterol esters in the cell (2). This pathway is altered in familial hypercholesterolemia (FH). The homozygous form of FH, in which LDL receptors are severely deficient (10%), occurs in only one subject out of every milion. Heterozygotes, with a consistent reduction of receptors (50%), represent one out of every 500 persons (3). Among patients with myocardial infarction under age 60 5% have a genetic defect of the LDL specific receptors (3). It happens therefore that coronary atherosclerosis, as well the others pictures of the clinical atherosclerosis, is mostly present in people having a normal receptorial system. The accumulation of cholesteryl esters in the foam cells, the peculiar trait of the atherosclerotic plaque, has to happen therefore through other pathways. Foam cells derive from two cellular sources: the arterial smooth muscle cells (SMC) and the monocytes-derived macrophages (MM) (4).