[Lipoprotein(a) as an athero-thrombotic risk factor: epidemiologic evidence and possible pathogenetic mechanisms]

Lipoprotein (a) [Lp(a)] has been known for more than 20 years as a peculiar "variant" of low-density lipoproteins (LDL), the recent interest for which mostly derives from its epidemiological and maybe pathogenetic link with coronary artery disease and atherosclerosis. The protein moiety of Lp(a)-apo(a)-is a glycoprotein produced by the liver, with evident structural analogies with plasminogen. A large variety of apo(a) isoforms have been described, with large variability in molecular weight, encoded by alleles located on chromosome 6. Plasma concentrations of Lp(a) are largely genetically determined, but variations on these levels are induced by changes in hepatic synthesis due to changes in control factors (for example in proteinuric syndromes). Many-but not univocal-epidemiological pieces of evidence indicate that high plasma concentrations of Lp(a) are associated with atherosclerosis and its cardiac, cerebral and peripheral manifestations, thereby potentially identifying a new cardiovascular risk factor, independent from plasma concentrations of LDL. This review will discuss such evidence and the mechanisms potentially linking Lp(a) and atherosclerosis. Proposed mechanisms include, among others, the susceptibility of Lp(a) to oxidation, the interference with mechanisms of fibrinolysis and the induction of endothelial activation.