[Metabolism and possible mechanisms of atherogenesis induced by lipoprotein (a)]

The mechanisms of atherogenesis are under intensive clinical and experimental investigation. It is commonly accepted that lipoproteins play a major role in atherogenesis. The results of several clinical studies suggest that lipoprotein (a) [Lp(a)] represents an independent risk factor for atherosclerosis. In order to obtain information on the physiological and pathological role of Lp(a), studies were undertaken to investigate the metabolism, removal sites, and possible atherogenic mechanisms of Lp(a). It was found that Lp(a) is not a metabolic product of other apoprotein B containing lipoproteins, but appears to be synthesized as a separate lipoprotein. The turnover parameters of Lp(a) resemble those of LDL. Binding studies of Lp(a) with cultured human fibroblasts demonstrated that Lp(a) is bound by the B-E receptor. After binding, Lp(a) is internalized and inhibits cellular cholesterol synthesis. In the presence of dextran sulfate or antibodies to the specific Lp(a) apoprotein or apoprotein B, Lp(a) is avidly taken up by macrophages. A similar mechanism might be responsible for the atherogenic effect of Lp(a).