Published Online
on February 16, 2004

A more recent version of this article appeared on February 24, 2004

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Submitted on July 8, 2003
Revised on October 30, 2003
Accepted on December 31, 2003

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, and Subodh Verma MD, PhD^*

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

^* To whom correspondence should be addressed. E-mail: subodh.verma{at}sympatico.ca.

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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