Reduction of thrombus formation in vivo using a thrombolytic agent targeted at damaged endothelial cells.
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.
Underwood
M J
MJ
Department of Cardiology, Glenfield General Hospital, Leicester, UK.
Pringle
S
S
de Bono
D P
DP
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
D000911:Antibodies, Monoclonal; D004338:Drug Combinations; D007074:Immunoglobulin G; D014568:Urokinase-Type Plasminogen Activator