Lipoprotein(a). Link between structure and pathology

It is now established that high plasma levels of lipoprotein(a) are associated with an increased risk of atherosclerotic cardiovascular disease. However, the mechanisms underlying this increased risk have not been elucidated. Lipoprotein(a) represents a class of lipoprotein particles having a cholesteryl ester-rich low-density lipoprotein (LDL)-like structure with a protein moiety represented by apolipoprotein B100 covalently linked to apolipoprotein(a), the specific marker of lipoprotein(a). Lipoprotein(a) particles with a triglyceride-rich core have also been described. Apolipoprotein(a) is a glycoprotein containing about 30% carbohydrates by weight, with a polypeptide chain highly polymorphic in size (300-700 kDa) and structurally similar to plasminogen. There appears to be a relation between apolipoprotein(a) size and lipoprotein(a) species. From a number of studies, it is becoming apparent that lipoprotein(a) can transverse the endothelium and accumulate in the arterial initima either extra- or intracellularly. Immunochemical evidence has also indicated that apolipoprotein(a) in the artery wall is colocalized with fibrin(ogen), suggesting that this complexation may have an atherogenic potential by promoting the transformation of resident macrophages into foam cells. This might also occur by the chemical modification of lipoprotein(a) by the action of either oxygen-free radicals, malondialdehyde, or interactions with matrix components. These findings invite the speculation that much of the apolipoprotein B detected in atherosclerotic lesions is contributed by lipoprotein(a). The role that lipoprotein(a) size and density heterogeneity and apolipoprotein(a) polymorphism might play in the intima accumulation of apolipoprotein B is not established.