Effect of Valsartan on extracellular matrix remodeling in rats with heart failure after myocardial infarction

Abstract

Objective To investigate the effect of Valsartan on Disintegrin metalloproteinases (ADAMs10,17) expressions in the process of heart failure (HF) after myocardial infarction (MI).MethodsAdult male Wistar rats weighing (200 ± 30) g were given humane care in compliance with the rules of the Animal Experimentation Committee of the first hospital of Harbin Medical University.And then the left anterior descending coronary artery was ligated.Based on UCG (LVEF ＜ 45％) Results The successfully MI-operated Wistar rats were divided randomly (random number) into three groups:HF group (HF group),placebo group (Pla group) and valsartan group (Val group).The rats in the Pla group and Val group were given the same volume of normal saline and valsartan 50 mg/ (kg · d),provided by Novartis company) by gavage.After 16 weeks,heart function was assessed by hemodynamic evaluation and serum TNF-α from LV cavity was measured by ELISA (R&D,USA).Muscle samples were extracted from the ischemic zone,and then the ADAMs 10,17 expressions were measured by immunoblotting.All the data were expressed by mean ± standard and evaluated by Student' s t test.Results After 16 weeks,the data of LV function including LVdp/dt LVdp/dtmin and LVSP were significantly improved in Val group than the others (P =0.006,P =0.015,P =0.003),and the LVEDP level was decreased (P =0.002).At the same time,the TNF-o level in the Val group was lower than that in the HF group (P =0.023).The ADAM17 and TNF-R1 expressions in the Val group was reduced compared with those in the HF group (P =0.01 1,P =0.022).However,ADAM10 expression is unchangeable in the four groups.Conclusions Valsartan may reduce the ADAM17 and TNF-R1 expressions in the ischemic zone,decrease the TNF-αconcentration and function in LV cavity so as to inhibit cardiac remodeling and improve heart function after MI. Key words: Valsartan ; Myocardial infarction ; Heart failure ; Tumor necrosis factor-α ; Tumor necrosis factor receptor; A disintegrin metalloproteinase; extracellular matrix remodeling; left ventricular function