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Effects of G-CSF on left ventricular remodeling and heart failure after acute myocardial infarction

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Abstract

Granulocyte colony-stimulating factor (G-CSF) is a hematopoietic cytokine that promotes proliferation and differentiation of neutrophil progenitors. G-CSF also possesses immunomodulatory properties. G-CSF-induced hematopoietic stem cell mobilization is widely used clinically for transplantation. After it was recently reported that G-CSF mobilizes bone marrow stem cells (BMSCs) into the infarcted hearts and accelerates the differentiation into vascular cells and cardiac myocytes, myocardial regeneration utilizing mobilization of BMSCs by G-CSF is attracting the attention of investigators. In animal models, G-CSF prevents left ventricular remodeling and dysfunction after acute myocardial infarction, at least in part, through a decrease in apoptotic cells and an increase in vascular cells. Although it is controversial whether BMSCs mobilized by G-CSF can differentiate into cardiac myocytes, G-CSF-induced angiogenesis is indeed recognized in infarcted heart. The cardioprotective effects of G-CSF are recognized even in isolated perfused heart. In addition, G-CSF activates various signaling pathways such as Akt, extracellular signal-regulated kinase, and Janus kinase 2/signal transducer and activator of transcription 3 through G-CSF receptors in cardiac myocytes. These observations suggest that G-CSF not only induces mobilization of stem cells and progenitor cells but also acts directly on cardiomyocytes. Therefore, G-CSF may be utilized as a novel agent to have protective and regenerative effects on injured myocardium. Although the effects of G-CSF on the progression of atherosclerosis are still unclear, there is a possibility that G-CSF will become a promising therapy for ischemic heart diseases.

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Abbreviations

AMI:

Acute myocardial infarction

BMSC:

Bone marrow stem cell

EC:

Endothelial cell

EPC:

Endothelial progenitor cell

ERK:

Extracellular signal-regulated kinase

G-CSF:

Granulocyte colony-stimulating factor

G-CSFR:

G-CSF receptor

GFP:

Green fluorescent protein

HSC:

Hematopoietic stem cell

Jak:

Janus kinase

LV:

Left ventricle

PCI:

Percutaneous coronary intervention

SCF:

Stem cell factor

SDF-1:

Stromal cell-derived factor-1

STAT:

Signal transducer and activator of transcription

VEGF:

Vascular endothelial growth factor

VSMC:

Vascular smooth muscle cell

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Authors and Affiliations

  1. Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan

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

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  1. Hiroyuki Takano
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  2. Yingjie Qin
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  3. Hiroshi Hasegawa
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Correspondence to Issei Komuro.

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Takano, H., Qin, Y., Hasegawa, H. et al. Effects of G-CSF on left ventricular remodeling and heart failure after acute myocardial infarction. J Mol Med 84, 185–193 (2006). https://doi.org/10.1007/s00109-005-0035-z

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