Apo(a) is a protein found covalently linked to apo-B100 in some LDL particles. Those LDL particles to which apo(a) is attached are called lipoprotein(a) or Lp(a). Plasma levels of Lp(a) correlate with increased cardiovascular disease risk in most populations, but not in African-Americans. The level of Lp(a) appears to be entirely genetically determined. The Lp(a) concentration is almost entirely related to the particular alleles of the Lp(a) gene expressed by an individual.
The Lp(a) gene is highly polymorphic (variable in structure). Thus, it appears that most individuals have different forms of the gene. The reason for this unusually high degree of genetic variability is that the gene comprises multiple repeat structures. Repeat structures lead to unequal crossing over during meiosis, causing the production of new variants of the gene in the offspring. The repeat structures are domains termed “kringle domains.” The kringle domain that is repeated in the apo(a) gene is homologous to a kringle domain of plasminogen, an enzyme involved in the dissolution of fibrin clots.
Why is Lp(a) so strongly correlated with risk of CHD? Because of its homology with plasminogen, it has been suggested that Lp(a) competes with plasmin for binding to fibrin clots and therefore would tend to be antithrombolytic. Another hypothesis is that Lp(a) might be atherogenic because it has been shown in vitro to stimulate smooth muscle cell proliferation, a hallmark of the atherosclerotic process.
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