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Am J Physiol Heart Circ Physiol (December 9, 2004). doi:10.1152/ajpheart.00963.2004
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Submitted on September 16, 2004
Accepted on November 30, 2004

Effect of C-Reactive Protein on Gene Expression in Vascular Endothelial Cells

Qingwei Wang1, Xiaojun Zhu1, Qin Xu1, Xia Ding1, Yuqing E. Chen1, and Qing Song1*

1 Cardiovascular Research Institute, Morehouse School of Medicine, Atlanta, Georgia, USA

* To whom correspondence should be addressed. E-mail: qsong{at}msm.edu.

C-reactive protein (CRP) is significantly associated with the risk of ischemic cardiovascular disease in epidemiological studies. To explore if CRP has a functional role, we investigated its effect on the gene expression profile of vascular endothelial cells. Human vascular endothelial cells (HUVEC and HAEC) were incubated with CRP at various concentrations (0-10 µg/ml). Microarray analysis showed that a total of 11 genes increased (IL-8, ZF9, Activin A, MCP-1, EXT1, Cited2, PAI-1, Fibronectin-1, Gravin, Connexin-43, and SORL- 1) and 6 genes decreased (MAT2A, WRB, RCN1, TEB4, DNCL1 and Annexin A1) by more than 2-fold on their mRNA levels. Interleukin-8 (IL-8) is the most significantly upregulated gene (13.6-fold), which demonstrated a clear dose and time-dependent pattern revealed by quantitative real-time PCR. Cell adhesion assay showed that CRP enhanced the monocyte adhesion to endothelial cell monolayer by 2-fold (P<0.01), which was partially blocked by an anti-IL-8 antibody (34.2% inhibition, P<0.01). Inhibition of ERK MAPK pathway using U0126 prevented CRP-induced IL-8 up-regulation, and Western blot analysis revealed a rapid activation of ERK1/2 after CRP stimulation. These data showed that CRP can significantly influence gene expressions in vascular endothelium. The CRP-responsive genes suggested that CRP may have a broad functional role in cell growth and differentiation, vascular remodeling and solid tumor development.




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