Role of metalloproteinases in rat cardiac extracellular matrix remodeling and effects of losartan on it

    BAI Jiangª²Tao, LU Fengª²Xiang, XU Di, CHEN Li, ZHOU Lei, YONG Yongª²Hong

    Department of Cardiology, First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China

    ¡¾Abstract¡¿ AIM: To investigate the role of metalloproteinase (MMPª²9), tissue inhibitor of metalloproteinase (TIMPª²1) and transforming growth factor¦Â1 (TGFª²¦Â1) in cardiac hypertrophy and extracellular matrix remodeling and the effects of Losartan on it in a rat model. METHODS: Male SD rats were randomly divided into three groups: control group, norepinephrine group (1.06 mg¡¤kg-1¡¤d-1¡Á15 d) and norepinephrine + Losartan group (10 mg¡¤kg-1¡¤d-1¡Á15 d). The rat cardiac hypertrophy models were established by intraperitoneal injection of norepinephrine (NE) twice a day for 15 days. Cardiac hypertrophy and extracellular matrix remodeling were evaluated by echocardiography and morphological examination. The mRNA and protein expression of matrix metalloproteinase (MMPª²9), tissue inhibitor of metalloproteinase (TIMPª²1) and transforming growth factor¦Â1 (TGFª²¦Â1) was examined by reverse transcriptionª²polymerase chain reaction (RTª²PCR) and immunohistochemical analysis. RESULTS: NEª²induced hypertrophy and extracellular matrix remodeling predominantly occurred in the left ventricular and the mRNA and protein expression of the MMPª²9, TIMPª²1 and TGFª²¦Â1 elevated (P<0.01). After Losartan treatment, the interventricular septal thickness, total collagen, type I, type III collagen and the expression of MMPª²9 and TGFª²¦Â1 decreased (P<0.01). CONCLUSION: MMPª²9, TIMPª²1 and TGFª²¦Â1 are involved in the cardiac extracellular matrix remodeling induced by NE. Losartan can prevent the cardiac hypertrophy and extracellular matrix remodeling, which is associated with the attenuation of myocardial MMPª²9 and TGFª²¦Â1. ......