Biochemical and Biophysical Research Communications, Vol.388, No.3, 606-611, 2009
Angiotensin II receptor blockade improves matrix metalloproteinases/tissue inhibitor of matrix metalloproteinase-1 balance and restores fibronectin expression in rat infarcted myocardium
Matrix metalloproteinases (MMPs) and the tissue inhibitors of MMPs (TIMPs) have been recognized to play a pivotal role in matrix remodeling following myocardial infarction (MI). The aims of the present study were to examine the expression profile of MMPs/TIMP-1 after MI and to determine whether angiotensin II receptor (ATR) blockade improves MMPs/TIMP-1 balance. Compared with sham-operated rats, in vivo MI-induced a significant elevation of MMP-2, MMP-3 and MMP-9 levels and a marked reduction of TIMP-1 and fibronectin (FN) expressions in infarcted left ventricular free wall (LVFW) and hypertrophic interventricular septum (IS) but not in non-infarcted right ventricle (RV). In addition, regional MI increased MMP-2, MMP-3 and MMP-9, while decreased TIMP-1 and FN in infarcted LVFW and hypertrophic IS compared with the non-infarcted RV. Compared with vehicle-treated MI rats, oral valsartan, but not PD123319, limited infarct size, normalized MMPs/TIMP-1 balance and restored FN level. The present findings might further our understanding of the regulatory mechanisms of valsartan in myocardial remodeling after MI. (C) 2009 Elsevier Inc. All rights reserved.
Keywords:Matrix metalloproteinases;Tissue inhibitors of matrix;metalloproteinases;Myocardial infarction;Myocardial remodeling;Fibronectin;Angiotensin II receptor blockade;Valsartan