Granulocyte colony-stimulating factor exacerbates cardiac fibrosis after myocardial infarction in a rat model of permanent occlusion.

Abstract

AIMS:

Controversy exists regarding the effects of granulocyte colony-stimulating factor (G-CSF) on post-infarction remodelling, which is regulated by matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). The aim of this study was to investigate the impact of G-CSF administration on cardiac MMP/TIMP ratios and long-term remodelling in a rat model of acute myocardial infarction (MI).

METHODS AND RESULTS:

Sprague-Dawley rats underwent coronary ligation to produce MI. Rats surviving the MI for 3 h were randomized to receive G-CSF (50 microg/kg/day for 5 consecutive days, n = 16) or saline (n = 10). Sham-operated animals received no treatment (n = 10). G-CSF injection significantly increased circulating white blood cells, neutrophils, and monocytes. Western blotting revealed that the ratios of MMP-2/TIMP-1 and MMP-9/TIMP-1 were significantly decreased in the infarcted myocardium. At 3 months, echocardiographic and haemodynamic examinations showed that the G-CSF treatment induced left ventricular (LV) enlargement and dysfunction. Histological analysis revealed that the extent of myocardial fibrosis and infarct size were larger in the G-CSF group than in the Saline group. Furthermore, G-CSF treated animals showed a significantly lower post-MI survival during the study period.

CONCLUSION:

Decrease of cardiac MMP/TIMP ratios by G-CSF after infarction may be important as a mechanism in promotion of myocardial fibrosis, which further facilitates infarct expansion and LV dysfunction.

• Authors: Zhaokang Cheng, Lailiang Ou, Yi Liu, Xiaolei Liu, Fei Li, Bin Sun, Yongzhe Che, Deling Kong, Yaoting Yu, Gustav Steinhoff
• Journal: Cardiovascular research (Cardiovasc Res) Vol. 80 Issue 3 Pg. 425-34 (Dec 01 2008) ISSN: 1755-3245 [Electronic] England
• PMID: 18676396 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Tissue Inhibitor of Metalloproteinase-1
• Transforming Growth Factor beta
• Granulocyte Colony-Stimulating Factor
• Matrix Metalloproteinase 2
• Matrix Metalloproteinase 9

Topics

• Animals
• Blood Pressure (drug effects)
• Coronary Occlusion (complications)
• Disease Models, Animal
• Female
• Fibrosis
• Granulocyte Colony-Stimulating Factor (adverse effects, pharmacology)
• Heart Ventricles (diagnostic imaging, metabolism, pathology)
• Leukocytes (pathology)
• Matrix Metalloproteinase 2 (metabolism)
• Matrix Metalloproteinase 9 (metabolism)
• Monocytes (pathology)
• Myocardial Infarction (etiology, metabolism, pathology)
• Myocardium (metabolism, pathology)
• Neutrophils (pathology)
• Rats
• Rats, Sprague-Dawley
• Tissue Inhibitor of Metalloproteinase-1 (metabolism)
• Transforming Growth Factor beta (metabolism)
• Ultrasonography
• Ventricular Remodeling (drug effects)