This Article Full Text Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bouchard, B. A. Articles by Tracy, P. B. Search for Related Content PubMed PubMed Citation Articles by Bouchard, B. A. Articles by Tracy, P. B.

(Arteriosclerosis, Thrombosis, and Vascular Biology. 1997;17:1-9.)
© 1997 American Heart Association, Inc.

Articles

Human Brain Pericytes Differentially Regulate Expression of Procoagulant Enzyme Complexes Comprising the Extrinsic Pathway of Blood Coagulation

Beth A. Bouchard; Marie A. Shatos; Paula B. Tracy

the Cell and Molecular Biology Program (B.A.B., M.A.S., P.B.T.) and the Department of Biochemistry (M.A.S., P.B.T.), University of Vermont College of Medicine, Burlington.

Correspondence to Paula B. Tracy, PhD, Department of Biochemistry, University of Vermont College of Medicine, Given Bldg C409, Burlington, VT 05405.

After vascular injury, pericytes may function in blood coagulation events that lead to thrombin formation due to their subendothelial location in the microvasculature. Pericytes from human cerebral cortex microvessels were isolated and characterized, and their ability to express and regulate procoagulant enzyme complexes was determined. Tissue factor was detected on the cell surface of cultured human brain pericytes by immunocytochemistry and was shown to form a functional complex with factor (F) VIIa to effect both FIX and FX activation. Treatment of pericytes with the calcium ionophore A23187 increased the observed tissue factor activity twofold to fivefold, which was shown to be due to an enhancement of cofactor activity and not the release of endogenous antigen stores. Pericytes also provided the appropriate membrane surface required for the assembly of a functional prothrombinase complex, so that in the presence of FVa and FXa, they effected thrombin formation 50 to 100 times faster than any other cell examined to date. In marked contrast to observations in other cell systems, pericyte expression of prothrombinase activity remained unaltered after treatment with A23187. As has been shown for platelets, the membrane receptor on pericytes for FXa assembly into the prothrombinase complex appears to at least partially consist of the FXa receptor effector cell protease receptor-1. These combined data indicate that pericytes can activate and propagate the coagulant response through the extrinsic pathway and that the activities of the required enzyme complexes can be differentially regulated in response to agonist stimulation. These observations support the concept that pericytes may play an important role in regulating coagulation events after cerebrovascular injury.

Key Words: pericytes • tissue factor • prothrombinase • effector cell protease receptor-1 • A23187

This article has been cited by other articles:

				M. Fisher Pericyte Signaling in the Neurovascular Unit Stroke, March 1, 2009; 40(3_suppl_1): S13 - S15. [Abstract] [Full Text] [PDF]

				N. Mackman, R. E. Tilley, and N. S. Key Role of the Extrinsic Pathway of Blood Coagulation in Hemostasis and Thrombosis Arterioscler. Thromb. Vasc. Biol., August 1, 2007; 27(8): 1687 - 1693. [Abstract] [Full Text] [PDF]

				R. Pawlinski, A. Fernandes, B. Kehrle, B. Pedersen, G. Parry, J. Erlich, R. Pyo, D. Gutstein, J. Zhang, F. Castellino, et al. Tissue factor deficiency causes cardiac fibrosis and left ventricular dysfunction PNAS, November 26, 2002; 99(24): 15333 - 15338. [Abstract] [Full Text] [PDF]

				J. Sevigny, C. Sundberg, N. Braun, O. Guckelberger, E. Csizmadia, I. Qawi, M. Imai, H. Zimmermann, and S. C. Robson Differential catalytic properties and vascular topography of murine nucleoside triphosphate diphosphohydrolase 1 (NTPDase1) and NTPDase2 have implications for thromboregulation Blood, April 15, 2002; 99(8): 2801 - 2809. [Abstract] [Full Text] [PDF]

				A. Papapetropoulos, P. Piccardoni, G. Cirino, M. Bucci, R. Sorrentino, C. Cicala, K. Johnson, V. Zachariou, W. C. Sessa, and D. C. Altieri Hypotension and inflammatory cytokine gene expression triggered by factor Xa-nitric oxide signaling PNAS, April 14, 1998; 95(8): 4738 - 4742. [Abstract] [Full Text] [PDF]

				M. P. Moyer, R. P. Tracy, P. B. Tracy, C. v.'t Veer, C. E. Sparks, and K. G. Mann Plasma Lipoproteins Support Prothrombinase and Other Procoagulant Enzymatic Complexes Arterioscler. Thromb. Vasc. Biol., March 1, 1998; 18(3): 458 - 465. [Abstract] [Full Text] [PDF]

				B. A. Bouchard, C. S. Catcher, B. R. Thrash, C. Adida, and P. B. Tracy Effector Cell Protease Receptor-1, a Platelet Activation-dependent Membrane Protein, Regulates Prothrombinase-catalyzed Thrombin Generation J. Biol. Chem., April 4, 1997; 272(14): 9244 - 9251. [Abstract] [Full Text] [PDF]