Background C-reactive protein (CRP), a new predictor of future cardiovascular diseases, has been reported to damage the vascular wall by inducing endothelial dysfunction and inflammation. This proatherogenic CRP was hypothesized to have a role in attenuating angiogenic functions of human endothelial progenitor cells (EPCs), possibly impairing vascular regeneration and increasing cardiovascular vulnerability to ischemic injury. Herein, we investigate the direct effect of CRP on angiogenic activity and gene expression in human EPCs. Methods and Results Human EPCs were incubated with human recombinant CRP(0 to 10 mg/L, 24 h, 37 째C), and their angiogenic activity and gene expression were determined by vascular endothelial growth factor-induced migration, adhesion to endothelial cells, Northern blotting assay, and ELISA for various growth factors and chemo-cytokines. Incubation of EPCs with CRP significantly inhibited EPC migration in response to vascular endothelial growth factor (51 짹 11 % reduction at 5 mg/L of CRP; n=6; p < 0.01), possibly by decreasing the expression of endothelial nitric oxide synthase and subsequent nitric oxide production. In addition, CRP reduced the adhesiveness of EPCs onto an endothelial cell monolayer (58 짹 6 % reduction at 5 mg/L of CRP; n=4; p < 0.01). When assayed for the gene expression of arteriogenic chemo-cytokines, CRP (7.5 mg/L) substantially decreased their expression levels in EPC, in part due to the upregulation of suppressors of cytokine signaling proteins. Conclusions These results suggest that CRP directly attenuates the angiogenic and possibly arteriogenic functions of EPCs. This CRP-induced EPC dysfunction may impair the vascular regenerative capacity of EPCs, thereby leading to increased risk of cardiovascular diseases.