Collagen-targeted antibodies inhibit platelet-dependent thrombosis in vivo

Abstract

Subendothelial collagen is one of the main triggers of platelet-dependent thrombus formation in arteries. The antithrombotic effects of rabbit polyclonal inhibitory antibodies to rat collagen type I-III and of murine non-inhibitory monoclonals to human recombinant single-/two-chain urokinase-type plasminogen activator (rscu-/rtcu-PA), cross-reacting with rat scu-/tcu-PA and their chemically synthesized conjugate, were studied both in vitro and in vivo. Anticollagen antibodies and bispecific conjugate inhibited human platelet adhesion, aggregation and formation of thrombus-like structures induced by rat collagen immobilized on the polystyrene surface in a condition mimicing a high shear rates in the large elastic arteries. Monoclonals to human rscu-/rtcu-PA did not block the collagen-induced platelet activation in vitro. The short-term treatment of the collagen-soaked silk thread by the collagen antibodies suppressed the platelet-dependent thrombus formation in the arterio-venous shunt in rats by 56 ± 4% (P<0.05). Bispecific conjugate, directed to collagen and endogenous rat scu-/tcu-PA 1inhibited thrombus formation by the same factor as anticollagen antibodies. The treatment of collagen-adsorbed conjugate by human rtcu-PA did not increase the antithrombotic effect. The present results suggest, that the local administration of the anticollagen antibodies to the site of vascular injury can be an efficient tool for prophylaxis of platelet-dependent thrombus formation in arteries at thrombolysis or percutaneous transluminal coronary angioplasty.