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.
Yang
Dachun
D
Department of Cardiology, General Hospital of PLA Chengdu Military Area Command, Chengdu 610083, PR China.
Ma
Shuangtao
S
Li
De
D
Tang
Bing
B
Yang
Yongjian
Y
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D005353:Fibronectins / Q000096:biosynthesis*; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D009203:Myocardial Infarction / Q000378:metabolism* / Q000473:pathology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000187:drug effects / Q000378:metabolism*; D013777:Tetrazoles / Q000494:pharmacology*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism*; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000068756:Valsartan
D047228:Angiotensin II Type 1 Receptor Blockers; D005353:Fibronectins; D007093:Imidazoles; D011725:Pyridines; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles; D019715:Tissue Inhibitor of Metalloproteinase-1; C073402:PD 123319; D000068756:Valsartan; D020782:Matrix Metalloproteinases; D014633:Valine