BINDING OF RECOMBINANT APOLIPOPROTEIN(A) TO EXTRACELLULAR-MATRIX PROTEINS

Elevated levels of lipoprotein(a), which consists of apolipoprotein(a) [apo(a)] covalently linked to a low-density lipoprotein-like moiety, is an independent risk factor for the development of atherosclerosis. We show that a recombinant form of apo(a) [r-apo(a)] binds strongly to fibronectin and fibrinogen, weakly to laminin, and not at all to von Willebrand factor, vitronectin, or collagen type IV. In contrast to th e binding of plasminogen to fibronectin, r-apo(a) binding does not app ear to be mediated by lysine-dependent interactions, based on the inab ility of E-aminocaproic acid concentrations up to 0.2 mol/L to signifi cantly decrease r-apo(a) binding to fibronectin. Plasminogen competed weakly for the binding of r-apo(a) to fibronectin, whereas r-apo(a) co mpletely abolished plasminogen binding. The 29- and 38-kd heparin-bind ing thermolysin fragments of fibronectin, previously identified as the lipoprotein(a) binding domains, were digested with trypsin, and a pep tide that retained the ability to bind r-apo(a) was isolated; the sequ ence of the peptide (AVTTIPAPTDLK) corresponds to the amino terminus o f the 29- and 38-kd domains. A synthetic peptide with this sequence wa s able to compete effectively with fibronectin for r-apo(a) binding.