|A significant correlation exists between elevated levels of lipoprotein(a) [Lp(a)] and the development of cardiovascular disease in human populations. The nature of this correlation is unclear, however, since the biological role of Lp(a) has not been determined. Lp(a) is distinguishable from low density lipoprotein (LDL) by the presence of apolipoprotein(a) [apo(a)] which likely renders the unique structural and functional properties attributed to Lp(a). Apo(a) is characterized by the presence of multiply-repeated copies of a sequence resembling plasminogen kringle IV.
The size of the repeated region in apo(a) is variable, giving rise to the occurrence of a number of differently sized isoforms in the population. Although apo(a) has been demonstrated to interact with a variety of plasma and cellular components, the biological relevance of these observations remains unknown.
My laboratory is engaged in studies addressing structure-function relationships in apo(a), using both molecular biology and protein chemistry techniques. This involves the analysis of recombinant forms of apo(a) expressed in mammalian cells. Using this model system, we are interested in addressing the following aspects of the biology of apo(a):
1.Analysis of the binding of apo(a) to macrophages, platelets, fibronectin, fibrin/fibrinogen, and endothelial cells.
2.Assembly of apo(a) into Lp(a) particles.
3.Effect of apo(a) on the fibrinolytic system (owing to its similarity to plasminogen).
4.Development of an animal model for Lp(a).
The eventual goal of our research is to determine the mechanism(s) by which Lp(a) exerts its effects, both in normal human physiology and in atherogenesis.