Lipoprotein(a) (Lp[a]), a newly recognized risk factor for atherosclerosis, contains a unique apolipoprotein [Apo(a)] which is genetically heterogeneous, particularly regarding the number of plasminogen Kringle 4-like domains. The remarkable homology between Lp(a) and plasminogen may serve as a link between atherosclerosis and thrombosis. The current project is designed to study: 1) the effects of apo(a) heterogeneity on its susceptibility to posttranslational modifications including oxidation, partial reduction and glycosylation 2) the effects of different Apo(a) isoforms and modifications on the capacity of Lp(a) to bind to various atherothrombotic components e.g. fibrin, endothelial cells, macrophages, platelets and subendothelial matrix; 3) the different domains involved in fibrinogen and fibrin interaction with Lp(a). La(a) with different apo(a) isoforms will be isolated from patients with premature atherosclerosis and controls. The effect of Apo(a) heterogeneity on the structure-function relationships will be tested using biochemical and immunological methods as well as cell culture techniques. The expected results may elucidate the relation between Apo(a) heterogeneity and the atherogenic potential of Lp(a).
