Background: It has been reported that granulocyte-colony stimulating factor(G-CSF) induces mobilization of bone marrow stem cells and has beneficial effects on cardiac remodeling after acute myocardial infarction(AMI). However, the use of G-CSF in coronary disease has raised safety concerns that it may impair endothelial function and increase cardiovascular events. Therefore, we investigated the effects of G-CSF on endothelial function.
Methods and Results: 98 subjects were divided into five groups; healthy-G-CSF(n=20), old MI(OMI)-control(20), OMI-G-CSF(20), AMI-control(20), and AMI-G-CSF(18). In both the healthy-G-CSF group and the OMI-G-CSF group, G-CSF increased serum C-reactive protein(CRP) (0.03짹0.05 vs. 0.61짹0.35 and 0.56짹0.38 vs 1.30짹0.77 mg/dl for baseline vs. post-G-CSF in the healthy group and OMI-G-CSF group respectively, p<0.001) and interleukin-6(IL-6) (7.4짹4.3 vs. 13.5짹7.8 and 17.9짹10.3 vs 27.5짹15.1 pg/dl for baseline vs. post-G-CSF in the healthy group and OMI-G-CSF group respectively, p<0.012 and p=0.023 respectively). In the AMI-G-CSF group, G-CSF hindered the decline of CRP during the recovery phase, resulting in a relative increase of CRP, when corrected for the natural change after AMI. However, in all three groups alike, G-CSF did not significantly alter flow-mediated dilation of the brachial artery. In vitro, G-CSF stimulated IL-6 secretion in monocytes, which induced CRP production in hepatocytes. However, G-CSF also increased the endothelial nitric oxide synthase(eNOS) mRNA expression and NO production, resulting in enhanced endothelial proliferation and function. When co-incubated CRP, G-CSF reversed the deleterious effects of CRP on endothelial cells.
Conclusions: Although G-CSF increased serum CRP, it did not deteriorate endothelial function in patients with MI. This phenomenon may be due to the dual opposing actions of G-CSF on endothelial cells; a negative effect of IL-6 mediated CRP induction and a positive effect of eNOS induction enhancing endothelial function.