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- Title
G-CSF prevents cardiac remodeling after myocardial infarction by activating the Jak-Stat pathway in cardiomyocytes.
- Authors
Harada, Mutsuo; Yingjie Qin; Takano, Hiroyuki; Minamino, Tohru; Yunzeng Zou; Toko, Haruhiro; Ohtsuka, Masashi; Matsuura, Katsuhisa; Sano, Masanori; Jun-ichiro Nishi; Iwanaga, Koji; Akazawa, Hiroshi; Kunieda, Takeshige; Weidong Zhu; Hasegawa, Hiroshi; Kunisada, Keita; Nagai, Toshio; Nakaya, Haruaki; Yamauchi-Takihara, Keiko; Komuro, Issei
- Abstract
Granulocyte colony-stimulating factor (G-CSF) was reported to induce myocardial regeneration by promoting mobilization of bone marrow stem cells to the injured heart after myocardial infarction, but the precise mechanisms of the beneficial effects of G-CSF are not fully understood. Here we show that G-CSF acts directly on cardiomyocytes and promotes their survival after myocardial infarction. G-CSF receptor was expressed on cardiomyocytes and G-CSF activated the Jak/Stat pathway in cardiomyocytes. The G-CSF treatment did not affect initial infarct size at 3 d but improved cardiac function as early as 1 week after myocardial infarction. Moreover, the beneficial effects of G-CSF on cardiac function were reduced by delayed start of the treatment. G-CSF induced antiapoptotic proteins and inhibited apoptotic death of cardiomyocytes in the infarcted hearts. G-CSF also reduced apoptosis of endothelial cells and increased vascularization in the infarcted hearts, further protecting against ischemic injury. All these effects of G-CSF on infarcted hearts were abolished by overexpression of a dominant-negative mutant Stat3 protein in cardiomyocytes. These results suggest that G-CSF promotes survival of cardiac myocytes and prevents left ventricular remodeling after myocardial infarction through the functional communication between cardiomyocytes and noncardiomyocytes.
- Subjects
GRANULOCYTE-colony stimulating factor; RECOMBINANT proteins; COLONY-stimulating factors (Physiology); HEART cells; MYOCARDIAL infarction; CORONARY disease; CARDIOLOGY
- Publication
Nature Medicine, 2005, Vol 11, Issue 3, p305
- ISSN
1078-8956
- Publication type
Article
- DOI
10.1038/nm1199