Published online before print April 3, 2003, doi: 10.1161/01.ATV.0000070100.47907.26
© 2003 American Heart Association, Inc.
ATVB In Focus |
Extracellular Mediators in Atherosclerosis and Thrombosis
Lessons From Thrombin Receptor Knockout Mice
From Johnson & Johnson Pharmaceutical Research and Development, L.L.C., Spring House, Pa.
Correspondence to Patricia Andrade-Gordon, Johnson & Johnson Pharmaceutical Research and Development, L.L.C., Welsh and McKean Roads, PO Box 776, Spring House, PA 19477-0776. E-mail pandrade{at}prdus.jnj.com
Series Editor: Marschall S. Brass
ATVB In Focus Extracellular Mediators in Artherosclerosis and Thrombosis
Previous Brief Reviews in this Series:
•Brasier AR, Recinos A III, Eledrisi MS. Vascular inflammation and the renin-angiotensin system. 2002;22:1257–1266.
•Moser M, Patterson C. Thrombin and vascular development: a sticky subject. 2003;23:922–930.
It is well appreciated that thrombin as well as other proteases can act as signaling molecules that specifically regulate cells by cleaving and activating members of a novel class of protease-activated receptors (PARs). The utility of gene knockout strategies to define and better comprehend the physiological role of specific proteins is perhaps best exemplified in the field of thrombin receptors. The development of PAR knockout mice has provided the unique opportunity to identify and characterize new members of this novel family of GPCRs, evaluate the interaction of PARs jointly expressed in common cells and tissues, and better understand the role of PARs in thrombosis, restenosis, vascular remodeling, angiogenesis, and inflammation. Presently, 4 members of the PAR family have been cloned and identified. In this review, we examine experimental evidence gleaned from PAR-/- mouse models as well as how the use of PAR-/- mice has provided insights toward understanding the physiological role of thrombin in cells of the vascular system and vascular pathology.
Key Words: thrombin receptor • protease-activated receptor • knockout mice • thrombosis • vascular biology
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