Journal of Molecular Medicine

, Volume 84, Issue 3, pp 185–193

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

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

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.

Keywords

Angiogenesis Cytokine G-CSF Heart failure Myocardial infarction Remodeling 

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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Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Hiroyuki Takano
    • 1
  • Yingjie Qin
    • 1
  • Hiroshi Hasegawa
    • 1
  • Kazutaka Ueda
    • 1
  • Yuriko Niitsuma
    • 1
  • Masashi Ohtsuka
    • 1
  • Issei Komuro
    • 1
  1. 1.Department of Cardiovascular Science and MedicineChiba University Graduate School of MedicineChibaJapan

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