Protein S as an in vivo cofactor to activated protein C in prevention of microarterial thrombosis in rabbits.
The antithrombotic effects of bovine activated protein C (APC) and protein S were investigated in a rabbit model of microarterial thrombosis. Because of the species specificity of the APC-protein S interaction, bovine APC expresses potent anticoagulant activity in rabbit plasma only when bovine protein S is also present. This provided a way to assess the contribution of bovine protein S to the antithrombotic effect of bovine APC. Rabbits were infused with boluses of activated protein C (0.1, 0.2, 0.4, or 0.8 mg/kg), protein S (0.5 mg/kg), or activated protein C (0.1 or 0.01 mg/kg) plus protein S (0.5 mg/kg). APC alone produced a dose-dependent antithrombotic effect, but only the group receiving the highest dose differed significantly from controls. While a low dose of activated protein C (0.1 mg/kg) alone had no antithrombotic effect, together with protein S (0.5 mg/kg) it produced a potent response. The presented results demonstrate the in vivo significance of protein S as a cofactor to activated protein C. The data show that a potent antithrombotic effect, without hemorrhagic side effects or significant systemic anticoagulation, may be achieved by low doses of activated protein C when combined with protein S.
Arnljots
B
B
Department of Plastic and Reconstructive Surgery, University of Lund, Malmö General Hospital, Sweden.
Dahlbäck
B
B
D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D002417:Cattle; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D011486:Protein C / Q000494:pharmacology* / Q000502:physiology; D017293:Protein S / Q000494:pharmacology* / Q000502:physiology; D011817:Rabbits; D015424:Reperfusion; D013927:Thrombosis / Q000517:prevention & control*; D013997:Time Factors
D011486:Protein C; D017293:Protein S