Background:The use of granulocyte-colony stimulating factor(G-CSF) in coronary disease has raised safety concerns that it may impair endothelial function. Therefore, we investigated the effects of G-CSF on endothelial function. Methods:This study was a substudy of the MAGIC cell-3-DES trial. 78 patients with acute myocardial infarction(AMI) or old MI(OMI) who underwent percutaneous coronary intervention(PCI) were prospectively enrolled and randomized into G-CSF group {G-CSF(10 關g/kg/day) injection for 3 days after PCI} or control group, and 20 healthy volunteers were enrolled. They were categorized into 5 groups; AMI-control(n=20), AMI-G-CSF(18), OMI-control(20), OMI-G-CSF(20), healthy-G-CSF(20). Baseline flow-mediated dilation(FMD) of brachial artery and serum inflammatory biomarkers were performed at day 1, and repeated at day 4 in all groups. In vitro, we also examined the direct effects of G-CSF on cultured endothelial cells(ECs) to elucidate the mechanism of G-CSF effects on endothelial function. Results:In both healthy-G-CSF and OMI-G-CSF group, G-CSF increased serum high sensitivity C-reactive protein(hsCRP)(p<0.001). In the AMI-G-CSF group, G-CSF hindered the decline of hsCRP during the recovery phase, resulting in a relative increase of hsCRP, when corrected for the natural change after AMI. However, in all three groups alike, G-CSF did not significantly alter FMD. As a plausible mechanism for this intriguing clinical finding, we demonstrated that G-CSF directly reversed the inhibitory effect of CRP on ECs via nitric oxide(NO). G-CSF directly increased both the transcription of eNOS and the phosphorylation of the eNOS protein leading to greater bioavailable NO, and decreased peroxynitrite formation without significant changes in superoxide production. Increase in eNOS mRNA was due to increased transcriptional activity rather than increased stability. Akt is the key signaling molecule by which G-CSF reversed the effect of CRP. Conclusions:Although G-CSF increased serum hsCRP, it did not deteriorate endothelial function in patients with MI. This phenomenon may be due to the dual opposing actions of G-CSF on ECs; a negative effect of CRP induction and a positive effect of eNOS induction via Akt.