title: Reduction of thrombus formation in vivo using a thrombolytic agent targeted at damaged endothelial cells.
abstract: Endothelial damage in saphenous vein harvested before coronary artery and peripheral vascular surgery has been well documented. Autogenous saphenous vein grafts are subject to early thrombotic occlusion, a process that is related to injury of this endothelial monolayer. A monoclonal antibody that binds to areas of endothelial damage (P14G11) and a non-specific immunoglobulin G (IgG) have been linked to urokinase. These conjugates were investigated in vivo using a rat vena cava model. The P14G11-urokinase conjugate significantly reduced thrombus formation compared with controls and non-conjugated urokinase (P < 0.02). No reduction in thrombus formation was seen with the IgG-urokinase conjugate. This shows that thrombus formation after endothelial damage in an in vivo model can be reduced with a targeted thrombolytic agent. Conjugates such as this may have a role in preventing early thrombotic occlusion in vein grafts.
authors.affiliation: Department of Cardiology, Glenfield General Hospital, Leicester, UK.
authors.forename: M J
authors.initials: MJ
authors.lastname: Underwood
authors.forename: S
authors.initials: S
authors.lastname: Pringle
authors.forename: D P
authors.initials: DP
authors.lastname: de Bono
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D001777:Blood Coagulation / Q000187:drug effects*; D004195:Disease Models, Animal; D004338:Drug Combinations; D004730:Endothelium, Vascular / Q000187:drug effects; D007074:Immunoglobulin G / Q000032:analysis; D051381:Rats; D015912:Thrombolytic Therapy; D013927:Thrombosis / Q000209:etiology*; D014568:Urokinase-Type Plasminogen Activator / Q000032:analysis / Q000276:immunology / Q000494:pharmacology*; D014684:Venae Cavae / Q000187:drug effects
chemical_list: D000911:Antibodies, Monoclonal; D004338:Drug Combinations; D007074:Immunoglobulin G; D014568:Urokinase-Type Plasminogen Activator