Granulocyte colony-stimulating factor mediates cardioprotection against ischemia/reperfusion injury via phosphatidylinositol-3-kinase/Akt pathway in canine hearts

Hiroyuki Takahama, Tetsuo Minamino, Akio Hirata, Akiko Ogai, Hiroshi Asanuma, Masashi Fujita, Masakatsu Wakeno, Osamu Tsukamoto, Ken Ichiro Okada, Kazuo Komamura, Seiji Takashima, Yoshiro Shinozaki, Hidezo Mori, Naoki Mochizuki, Masafumi Kitakaze

Research output: Contribution to journalArticlepeer-review

39 Citations (Scopus)

Abstract

Purpose: Recent studies suggest that G-CSF prevents cardiac remodeling following myocardial infarction (MI) likely through regeneration of the myocardium and coronary vessels. However, it remains unclear whether G-CSF administered at the onset of reperfusion prevents ischemia/reperfusion injury in the acute phase. We investigated acute effects of G-CSF on myocardial infarct size and the incidence of lethal arrhythmia and evaluated the involvement of the phosphatidylinositol-3 kinase (PI3K) in the in vivo canine models. Methods: In open-chest dogs, left anterior descending coronary artery (LAD) was occluded for 90 minutes followed by 6 hours of reperfusion. We intravenously administered G-CSF (0.33 μ/kg/min) for 30 minutes from the onset of reperfusion. Wortmannin, a PI3K inhibitor, was selectively administered into the LAD after the onset of reperfusion. Results: G-CSF significantly (p<0.05) reduced myocardial infarct size (38.7±4.3% to 15.7±5.3%) and the incidence of ventricular fibrillation during reperfusion periods (50% to 0%) compared with the control. G-CSF enhanced Akt phospholylation in ischemic canine myocardium. Wortmannin blunted both the infarct size-limiting and anti-arrhythmic effects of G-CSF. G-CSF did not change myeloperoxidase activity, a marker of neutrophil accumulation, in the infarcted myocardium. Conclusion: An intravenous administration of G-CSF at the onset of reperfusion attenuates ischemia/reperfusion injury through PI3K/Akt pathway in the in vivo model. G-CSF administration can be a promising candidate for the adjunctive therapy for patients with acute myocardial infarction.

Original languageEnglish
Pages (from-to)159-165
Number of pages7
JournalCardiovascular Drugs and Therapy
Volume20
Issue number3
DOIs
Publication statusPublished - 2006 Jun
Externally publishedYes

Keywords

  • Akt
  • G-CSF
  • Ischemia-reperfusion injury
  • Myocardial infarction
  • Phosphatidylinositol-3 kinase
  • Ventricular fibrillation

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine
  • Pharmacology (medical)

Fingerprint

Dive into the research topics of 'Granulocyte colony-stimulating factor mediates cardioprotection against ischemia/reperfusion injury via phosphatidylinositol-3-kinase/Akt pathway in canine hearts'. Together they form a unique fingerprint.

Cite this