Biochemistry of Lipoprotein (a)
- Molecular mass: 200 to 700kD
- Plasma concentration: < 0.5mg/dl to 200mg/dl (40 to 50% genetically determined, nearly constant throughout life)
- Normal range: < 30mg/dl
Lipoprotein (a) is among the newly classified sub-classes of “Low-density Lipoproteins (LDL)”. The Lp(a) lipid composition is similar to that of LDL. Whereas the LDL particle contains an additional apoprotein called apoB100, the Lp(a) particle contains an additional apoprotein called apo(a), which is linked to the apoB by means of a disulfide bridge. Apo(a) is highly homologous to plasminogen, except for one recognition sequence for plasminogen activators that is lacking in Lp(a).
Clinical significance of Lp(a)
Recently an impressive body of data has been accumulated to establish that Lp(a) is an independent risk factor for coronary heart disease (CHD): Concentrations of Lp(a) > 30 mg/dl have been correlated directly with premature CHD, especially when LDL levels are elevated. The risk for stroke as well as for re-stenosis after coronary artery bypass surgery reportedly correlates highly with the increases in Lp(a). The striking homology between Lp(a) and plasminogen has given rise to the hypothesis that the increased risk of premature atherosclerosis and thrombotic diseases associated with elevated Lp(a) levels arises from the molecular mimicry of plasminogen by apo(a). Lp(a) competes with plasminogen for the plasminogen receptor present on a variety of cells including the endothelial cells of the aortic wall. Plasminogen cannot be activated properly and fibrinolysis is impaired. The chronic formation and stabilization of mural thrombi is believed to play a key role in the progression and growth of atherosclerotic lesions, and acute thrombotic events often occur on the fissures of atherosclerotic plaques.
Clinical or Research use of Lp(a)
- Premature coronary heart disease (CHD)
- Familial cardiovascular diseases
- After coronary artery bypass surgery
- In subjects with cardiovascular diseases in the absence of other risk factors
- Suspected elevated Lp(a) levels in subjects with hypercholesterolemia resistant against statin therapy