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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:e108.)
© 2006 American Heart Association, Inc.

Vascular Biology

Granulocyte Colony Stimulating Factor Directly Inhibits Myocardial Ischemia-Reperfusion Injury Through Akt–Endothelial NO Synthase Pathway

Kazutaka Ueda; Hiroyuki Takano; Hiroshi Hasegawa; Yuriko Niitsuma; Yingjie Qin; Masashi Ohtsuka; Issei Komuro

From the Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine, Japan.

Correspondence to Issei Komuro, MD, PhD, Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan. E-mail komuro-tky{at}umin.ac.jp

Objective— Granulocyte colony stimulating factor (G-CSF) has been reported recently to prevent cardiac remodeling and dysfunction after acute myocardial infarction through signal transducer and activator of transcription 3 (STAT3). In this study, we examined acute effects of G-CSF on the heart against ischemia-reperfusion injury.

Methods and Results— Rat hearts were subjected to global 35-minute ischemia and 120-minute reperfusion in Langendorff system with or without G-CSF (300 ng/mL). G-CSF administration was started at the onset of reperfusion. Triphenyltetrazolium chloride staining revealed that G-CSF markedly reduced the infarct size. G-CSF strongly activated Janus kinase 2 (Jak2), STAT3, extracellular signal-regulated kinase (ERK), Akt, and endothelial NO synthase (NOS) in the hearts subjected to ischemia followed by 15-minute reperfusion. The G-CSF–induced reduction in infarct size was abolished by inhibitors of phosphatidylinositol 3-kinase, Jak2, and NOS but not of mitogen-activated protein kinase kinase (MEK).

Conclusions— These results suggest that G-CSF acts directly on the myocardium during ischemia-reperfusion injury and has acute nongenomic cardioprotective effects through the Akt–endothelial NOS pathway.

Granulocyte colony stimulating factor (G-CSF) has been reported recently to prevent cardiac remodeling and dysfunction after acute myocardial infarction. In this study, we demonstrated in isolated rat hearts that G-CSF administered after reperfusion directly protects the heart from myocardial ischemia-reperfusion injury through the Akt–eNOS pathway.

Key Words: G-CSF • reperfusion injury • cytokine • nitric oxide synthase • signal transduction

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