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(Circulation. 2004;109:833-836.)
© 2004 American Heart Association, Inc.

Brief Rapid Communications

C-Reactive Protein Upregulates Complement-Inhibitory Factors in Endothelial Cells

Shu-Hong Li, MSc^*; Paul E. Szmitko, BSc^*; Richard D. Weisel, MD; Chao-Hung Wang, MD; Paul W.M. Fedak, MD, PhD; Ren-Ke Li, MD, PhD; Donald A.G. Mickle, MD; Subodh Verma, MD, PhD

From the Division of Cardiac Surgery, University of Toronto, Ontario, Canada.

Correspondence to Subodh Verma, MD, PhD, Division of Cardiac Surgery, Toronto General Hospital, 14EN-215, 200 Elizabeth St, Toronto, Ontario, Canada M5G 2C4. E-mail subodh.verma{at}sympatico.ca

Received July 8, 2003; de novo received October 30, 2003; accepted December 31, 2003.

Background— Because complement-mediated vascular injury participates in atherosclerosis and C-reactive protein (CRP) can activate the complement cascade, we sought to determine whether CRP affects the expression of the protective complement-inhibitory factors on the cell surface of endothelial cells (ECs).

Methods and Results— Human coronary artery or human saphenous vein ECs were incubated with CRP (0 to 100 µg/mL, 0 to 72 hours), and the expression of the complement-inhibitory proteins decay-accelerating factor (DAF), membrane cofactor protein (CD46), and CD59 were measured by flow cytometry. Incubation with CRP resulted in a significant increase in the expression of all 3 proteins. CRP-induced upregulation of DAF required increased steady-state mRNA and de novo protein synthesis. The increased expression of complement-inhibitory proteins was functionally effective, resulting in significant reduction of complement-mediated lysis of antibody-coated human saphenous vein ECs.

Conclusions— These observations provide evidence for a possible protective role for CRP in atherogenesis.

Key Words: endothelium • atherosclerosis • proteins

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