Lipoprotein(a): its inheritance and molecular basis of its atherothrombotic role

Lipoprotein(a) or Lp(a), is a member of the plasma lipoproteins with general properties of LDL but with a protein moiety represented by apoB100 disulfide linked to apolipoprotein(a) or apo(a). Apo(a) is polymorphic in size; at present a total of 11 isoforms have been reported, but more are likely to be identified in view of the fact that at least 19 alleles of the apo(a) gene have recently been reported. There are remarkable variations in the plasma Lp(a) levels; but uncertainties still exist about the factors responsible for this variability. High plasma Lp(a) levels have been associated with an increased incidence of cardiovascular disease, mainly based on epidemiological evidence. Both atherogenic and thrombogenic potentials have been suggested; the first attributable to the LDL-like properties of Lp(a) and the other to the plasminogen-like characteristics of apo(a). From the mechanistic viewpoint in vitro studies suggest that the thrombogenic action may occur at the level of the endothelium whereas Lp(a) that localizes in the sub-endothelial intima is expected to undergo complexation with matrix components and favor the formation of the atherosclerotic plaque. How Lp(a) polymorphism relates to the postulated cardiovascular pathogenicity of this lipoprotein remains to be established.