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

Zhaokang Cheng, Lailiang Ou, Yi Liu, Xiaolei Liu, Fei Li, Bin Sun, Yongzhe Che, Deling Kong, Yaoting Yu, Gustav Steinhoff
2008 Cardiovascular Research  
Aims Controversy exists regarding the effects of granulocyte colony-stimulating factor (G-CSF) on postinfarction 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.
more » ... on to produce MI. Rats surviving the MI for 3 h were randomized to receive G-CSF (50 mg/kg/day for 5 consecutive days, n ¼ 16) or saline (n ¼ 10). Sham-operated animals received no treatment (n ¼ 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.
doi:10.1093/cvr/cvn202 pmid:18676396 fatcat:qtpjlsqgkfb7llzrz24ge7ybtu