Macrophage colony-stimulating factor improves cardiac function after ischemic injury by inducing vascular endothelial growth factor production and survival of cardiomyocytes

Tatsuma Okazaki, Satoru Ebihara, Masanori Asada, Shinsuke Yamanda, Yoshifumi Saijo, Yasuyuki Shiraishi, Takae Ebihara, Kaijun Niu, He Mei, Hiroyuki Arai, Tomoyuki Yambe

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Macrophage colony-stimulating factor (M-CSF), known as a hematopoietic growth factor, induces vascular endothelial growth factor (VEGF) production from skeletal muscles. However, the effects of M-CSF on cardiomyocytes have not been reported. Here, we show M-CSF increases VEGF production from cardiomyocytes, protects cardiomyocytes and myotubes from cell death, and improves cardiac function after ischemic injury. In mice, M-CSF increased VEGF production in hearts and in freshly isolated cardiomyocytes, which showed M-CSF receptor expression. In rat cell line H9c2 cardiomyocytes and myotubes, M-CSF induced VEGF production via the Akt signaling pathway, and M-CSF pretreatment protected these cells from H2O2-induced cell death. M-CSF activated Akt and extracellular signal-regulated kinase signaling pathways and up-regulated downstream anti-apoptotic Bcl-xL expression in these cells. Using goats as a large animal model of myocardial infarction, we found that M-CSF treatment after the onset of myocardial infarction by permanent coronary artery ligation promoted angiogenesis in ischemic hearts but did not reduce the infarct area. M-CSF pretreatment of the goat myocardial infarction model by coronary artery occlusion-reperfusion improved cardiac function, as assessed by hemodynamic parameters and echocardiography. These results suggest M-CSF might be a novel therapeutic agent for ischemic heart disease.

Original languageEnglish
Pages (from-to)1093-1103
Number of pages11
JournalAmerican Journal of Pathology
Volume171
Issue number4
DOIs
Publication statusPublished - 2007 Oct

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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