Citations to this article

Protein S as an in vivo cofactor to activated protein C in prevention of microarterial thrombosis in rabbits.
B Arnljots, B Dahlbäck
B Arnljots, B Dahlbäck
Published May 1, 1995
Citation Information: J Clin Invest. 1995;95(5):1987-1993. https://doi.org/10.1172/JCI117883.
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Research Article

Protein S as an in vivo cofactor to activated protein C in prevention of microarterial thrombosis in rabbits.

Abstract

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.

Authors

B Arnljots, B Dahlbäck

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Citations to this article (19)

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WE Plautz, VS Pilli, BC Cooley, R Chattopadhyay, PR Westmark, T Getz, D Paul, W Bergmeier, JP Sheehan, R Majumder 		Arteriosclerosis, thrombosis, and vascular biology 2018
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GJ Vlachojannis, V Kunadian, JM Sweeny, R Mehran 		Therapeutic Advances in Thrombosis: De Caterina/Therapeutic Advances in Thrombosis 2012
Species-specific anticoagulant and mitogenic activities of murine protein S
JA Fernández, MJ Heeb, X Xu, I Singh, BV Zlokovic, JH Griffin 		Haematologica 2009
Protein C and the postresuscitation syndrome -improvement of neurological outcome after cardiac arrest in rats
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Human activated protein C variants in a rat model of arterial thrombosis
K Malm, B Arnljots, B Dahlbäck 		Thrombosis Journal 2008
Antithrombotic and anticoagulant effects of wild type and Gla-domain mutated human activated protein C in rats
K Malm, B Arnljots, IM Persson, B Dahlbäck 		Thrombosis Research 2007
Factor V and Thrombotic Disease: Description of a Janus-Faced Protein
GA Nicolaes, B Dahlbäck 		Arteriosclerosis, thrombosis, and vascular biology 2002
Active site-inactivated factor VIIa prevents thrombosis without increased surgical bleeding: Topical and intravenous administration in a rat model of deep arterial injury
T Söderström, U Hedner, B Arnljots 		Journal of Vascular Surgery 2001
Effect of locally-applied active site-blocked activated factor VII (ASIS) on experimental arterial thrombosis
B Arnljots, T Söderström, M Ezban, U Hedner 		Blood Coagulation & Fibrinolysis 2000
Antithrombotic and Platelet Activating Effects of Heparin in Prevention of Microarterial Thrombosis
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Prevention of experimental arterial thrombosis by topical administration of active site–inactivated factor VIIa
B Arnljots, M Ezban, U Hedner 		Journal of Vascular Surgery 1997
The Thrombomodulin/Protein C/Protein S Anticoagulant Pathway Modulates the Thrombogenic Properties of the Normal Resting and Stimulated Endothelium
Y Cadroy, A Diquélou, D Dupouy, JP Bossavy, KS Sakariassen, P Sié, B Boneu 		Arteriosclerosis, thrombosis, and vascular biology 1997
Species specificity of anticoagulant activity of activated human protein C. Involvement of factor V as well as protein S
Y Katsuura, T Mochizuki, M Tamura, S Hoshide, M Kiyoki, T Nakagaki, S Miyamoto 		Thrombosis Research 1996
Actuated protein C resistance: From phenotype to genotype and clinical practice
A Hillarp, B Dahlbäck, B Zöller 		Blood Reviews 1995
Antithrombotic Effects of Activated Protein C and Protein S in a Rabbit Model of Microarterial Thrombosis
B Arnljots, B Dahlbäck 		Arteriosclerosis, thrombosis, and vascular biology 1995

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