NOVEL INTERACTION OF APOLIPOPROTEIN(A) WITH BETA-2-GLYCOPROTEIN-I MEDIATED BY THE KRINGLE-IV-DOMAIN

Lipoprotein(a) [Lp(a)], which has been shown to interact with fibrin(o gen) and other components of the blood clotting cascade, is a major in dependent risk factor for atherothrombotic disease in humans. The phys iological function(s) of Lp(a), as well as the precise mechanism(s) by which high plasma levels of Lp(a) increase risk are unknown. identifi cation of further potential apo(a)-protein ligands may be crucial to i lluminate apo(a)'s function(s) and pathophysiological properties. We u sed the repetitive apo(a) kringle IV type 2, which is variable in numb er in apo(a), to screen a human liver cDNA library by the yeast two-hy brid interaction trap system. Among 11 positive crones that emerged fr om the screen, eight clones were identified as beta-2 glycoprotein 1 a nd one as fibronectin. Coimmunoprecipitation experiments confirmed tha t beta-2 glycoprotein I and apo(a)/Lp(a) interact in human plasma and in cell culture supernatants of COS-1 cells, which ectopically express ed apo(a). The apo(a)-beta 2-glycoprotein I interaction indicates new potential roles for Lp(a) in fibrinolysis and autoimmunity. (C) 1997 b y The American Society of Hematology.