Granulocyte-macrophage colony-stimulating factor inducer accelerates post-myocardial infarction remodeling

Abstract

Background: Granulocyte-macrophage colony-stimulating factor (GM-CSF) modifies wound healing by promoting monocytopoiesis and infiltration of monocytes and macrophages into injured tissue; however, the effect of GM-CSF induction on the infarct healing process and myocardial fibrosis is unclear. Methods: A myocardial infarction (MI) model was produced in Wistar rats by ligation of the left coronary artery. Animals after MI were randomized to receive GM-CSF inducer (romurtide 200 μg/kg/day for 7 consecutive days, MI/Ro) or saline (MI/C). Results: Echocardiographic and hemodynamic studies on day 14 revealed increased left ventricular (LV) end-diastolic dimension, decreased fractional shortening and elevated LV end-diastolic pressure in MI/Ro compared with MI/C. Immunoblotting showed that expression of transforming growth factor-beta1 (TGF-β1) in the infarcted site on day 3 was decreased in MI/Ro compared with MI/C. In the infarcted site, TGF-β1, collagen type I and type III mRNA expression on day 3 and collagen content on day 7 were reduced in MI/Ro compared with MI/C, in association with marked infarct expansion. In MI/Ro, monocyte chemoattractant protein-1 mRNA level and the degree of infiltration of monocyte-derived macrophages (ED-1-positive) were greater in the infarcted site on day 7 than those in MI/C. Conclusions: GM-CSF induction by romurtide facilitated infarct expansion in association with the promotion of monocyte recruitment and inappropriate collagen synthesis in the infarcted region during the early phase of MI.