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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28:698.)
© 2008 American Heart Association, Inc.

Cell Biology/Signaling

C-Reactive Protein Enhances Tissue Factor Expression by Vascular Smooth Muscle Cells

Mechanisms and In Vivo Significance

Jianbo Wu; Meredith J. Stevenson; Jordan M. Brown; Elizabeth A. Grunz; Tammy L. Strawn; William P. Fay

From the Department of Internal Medicine, University of Missouri School of Medicine, and Research Service, Harry S. Truman Memorial Veterans Affairs Hospital, Columbia, MO.

Correspondence to Jianbo Wu, MD, PhD, University of Missouri, MC314 McHaney Hall, One Hospital Drive DC095.00, Columbia, Missouri 65212. E-mail wuji{at}health.missouri.edu

Objective— We examined the impact of C-reactive protein (CRP) on vascular smooth muscle cell (VSMC) expression of tissue factor (TF) and TF pathway inhibitor (TFPI).

Methods and Results— TF mRNA, protein, and activity levels were significantly higher in VSMCs isolated from CRP-transgenic (Tg) mice than from wild-type (WT) mice. TFPI expression was significantly downregulated in CRP-Tg versus WT VSMCs. Transfection of human VSMCs with CRP expression plasmid significantly increased TF expression and decreased TFPI expression. Gene silencing of Fc receptor IIIa (FcRIIIa) blocked the effect of CRP on VSMC TF expression. CRP activated p44/42, but not p38 or JNK MAP kinase (MAPK), and the effect of CRP on TF expression was blocked by pharmacological inhibitor of p44/42, but not p38 or JNK MAPK. Reactive oxygen species (ROS) scavengers blocked CRP-induced upregulation of VSMC TF expression. In vivo analyses revealed significant increases in TF expression and decreases in TFPI expression in carotid arteries of CRP-Tg mice versus WT mice.

Conclusion— CRP increases TF and decreases TFPI expression by VSMCs in vitro and in vivo. Induction of TF expression by CRP is mediated by FcRIIIa, p44/42 MAPK, and ROS generation. These data offer important insights into the role of CRP in the pathogenesis of arterial thrombosis.

We show that upregulation of C-reactive protein (CRP) expression increases tissue factor (TF) expression while decreasing TF pathway inhibitor expression in vascular smooth muscle cells, both in vitro and in vivo. Induction of TF expression by CRP is mediated by Fc receptor IIIa, p44/42 MAP kinase, and reactive oxygen species generation.

Key Words: C-reactive protein • tissue factor • VSMC • thrombosis

Related Article:

Does Tissue Factor Expression by Vascular Smooth Muscle Cells Provide a Link Between C-Reactive Protein and Cardiovascular Disease?

Nigel Mackman and Mark B. Taubman
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