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(Circulation Research. 2007;100:155.)
© 2007 American Heart Association, Inc.

Editorials

Endothelial Cell Protein C Receptor

Role Beyond Endothelium?

Meenakshisundaram Thiyagarajan, Tong Cheng, Berislav V. Zlokovic

From the Frank P. Smith Laboratory for Neuroscience and Neurosurgical Research (M.T., T.C., B.V.Z.), Department of Neurosurgery, University of Rochester Medical Center, NY.

Correspondence to Berislav V. Zlokovic, MD, PhD, University of Rochester Medical Center, 601 Elmwood Avenue, Box 645, Rochester, New York 14642. E-mail berislav_zlokovic@urmc.rochester.edu

See related article, pages 255–262

Key Words: endothelial protein C receptor • activated protein C • protease activated receptor-1 • endothelium • vascular smooth muscle cells

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Endothelial cell protein C receptor (EPCR) is a type 1 transmembrane glycoprotein with homology to the major histocompatibility complex (MHC)-class 1/CD1 family of molecules.¹ EPCR was isolated and cloned as an endothelial cell-specific, high selectivity and high affinity binding protein for protein C (PC) and activated PC (APC).¹ EPCR binds PC on the endothelial surface and presents it to the thrombin:thrombomodulin (TM) complex for activation (Figure 1). Thrombin bound to TM proteolytically activates PC and generates APC which exerts independent anticoagulant and cellular activities.² The APC anticoagulant pathway is mediated by proteolytic inactivation of blood coagulation Factors Va and VIIIa with the contribution of several cofactors, including protein S, high density lipoproteins, phosphatidylserine, cardiolipin, and glucosylceramide to name a few. The APC cellular pathway on endothelium requires EPCR and the protease activated receptor-1 (PAR-1)³ which mediates APC’s cytoprotective effects, including alterations in gene expression profiles, antiapoptotic activity, antiinflammatory activity and protection of endothelial barriers^4–10 (Figure 1). EPCR also regulates endogenous physiologic activation of PC by thrombin which is linked to PAR-1-dependent APC protective autocrine signaling in endothelium.¹¹

View larger version (27K):   Figure 1. EPCR binds protein C (PC) on endothelium and presents it to TM (thrombomodulin)-thrombin complex for activation by thrombin. Activated PC (APC) dissociates from EPCR and TM-thrombin complexes and inactivates coagulation factors Va and VIIIa into inactive forms Vi and VIIIi promoting anticoagulation. APC bound to EPCR activates the protease activated receptor-1 (PAR-1) which binds the Gq and Gi proteins to activate phosophlipase(s) (PLC) in SMCs and endothelium . . . [Full Text of this Article]

Related Article:

Human Vascular Smooth Muscle Cells Express Functionally Active Endothelial Cell Protein C Receptor

Ellen Bretschneider, Barbara Uzonyi, Artur-Aron Weber, Jens W. Fischer, Robert Pape, Katharina Lötzer, and Karsten Schrör
Circ. Res. 2007 100: 255-262. [Abstract] [Full Text] [PDF]

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