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Review
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Korean J Med. 2006;71(1):288-288.
- The Effect of Granulocyte-Colony Stimulating Factor on Endothelial Function - Dual Opposing Actions of G-CSF on CRP and eNOS
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- The Effect of Granulocyte-Colony Stimulating Factor on Endothelial Function - Dual Opposing Actions of G-CSF on CRP and eNOS
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1Department of Internal Medicine, Hanyang University College of Medicine, Seoul; 2Department of Life Science, Postech Biotech Center, Pohang University of Science and Technology, Pohang, Korea
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- Abstract
- 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
μg/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.
Keywords :
