Selective Down-Regulation of Extracellular Matrix Gene Expression by Bone Marrow Derived Stem Cell Transplantation Into Infarcted Myocardium

Abstract

Myocardial fibrosis is a major component of ventricular remodeling after myocardial infarction (MI). The aim of the present study was to determine the outcome of transplantation into ischemic myocardium of bone marrow derived stem cell (MSC) on left ventricular (LV) function and remodeling, and to look closely at extracellular matrix gene expression. MI was induced by direct ligation of the left anterior descending coronary artery in rats, followed by MSC transplantation into the ischemic myocardium. Hemodynamic evaluations were performed at 7 and 28 days after coronary ligation. Changes in the mRNA expressions of collagen type I and type III, matrix metalloproteinase-1, tissue inhibitor of matrix metalloproteinase (TIMP)-1 and transforming growth factor (TGF)-beta(1) were investigated using reverse transcription polymerase chain reaction and in situ hybridization after MI. Heart/body weight ratio in the MI + MSC group decreased after coronary ligation. However, LV systolic pressure and LV peak velocities of contraction and relaxation significantly increased compared with the MI group (p<0.01). There was marked up-regulation of the mRNA expressions of collagen types I and III, TIMP-1 and TGF-beta(1) in the MI rats, all of which were significantly attenuated by MSC transplantation. MSC transplantation could inhibit LV remodeling, improve heart function and reduce the expression of extracellular matrix genes.