Improvement in Cardiac Function With Small Intestine Extracellular Matrix Is Associated With Recruitment of C-Kit Cells, Myofibroblasts, and Macrophages After Myocardial Infarction

Objectives This study tested the hypothesis that modulation of angiogenesis and cardiac function by injecting small intestine extracellular matrix emulsion (EMU) into myocardium is associated with recruitment of c-kit cells, myofibroblasts, and macrophages after myocardial infarction. Background Degradation of native extracellular matrix has been associated with adverse cardiac remodeling after infarction. Methods Sixty-four rats were subjected to 45 min ischemia followed by 3, 7, 21, and 42 days of reperfusion, respectively. Saline or EMU (30 to 50 mu l) was injected into the area at risk myocardium after reperfusion. Histological examination was performed by immunohistochemical staining, and cardiac function was analyzed using echocardiography. Results The population of c-kit-positive cells in infarcted myocardium with the EMU injection increased significantly relative to the saline control at 7 days of reperfusion. Along with this change, alpha-smooth muscle actin expressing myofibroblasts and macrophages accumulated to a significant extent compared with the saline control. Increased vascular endothelial growth factor protein level and strong immunoreactivity of vascular endothelial growth factor expression were observed. Angiogenesis in the EMU area was significantly enhanced relative to the saline control, evidenced by increased density of alpha-smooth muscle actin positive vessels. Furthermore, echocardiography showed significant improvements in fractional shortening, ejection fraction, and stroke volume in the EMU group. The wall thickness of the infarcted middle anterior septum in the EMU group was significantly increased relative to the saline control. Conclusions We show for the first time that injection of EMU into the infarcted myocardium increases neovascularization and preserves cardiac function, potentially mediated by enhanced recruitment of c-kit-positive cells, myofibroblasts, and macrophages. (J Am Coll Cardiol 2010; 55: 1250-61) (C) 2010 by the American College of Cardiology Foundation