Telmisartan reverses myocardial fibrosis by regulating the expression of Krüppel-like factor 4

Objective To explore the change and the effect of telmisartan on Kruppel-like factor 4 and its related factors in SHR rats myocardial fibrosis. Methods Ten-week-old male SHR rats were fed standard chow diet and treated with telmisartan (10 mg·kg-1·day-1) for 8 weeks, while WKY rats are used as control, fed standard chow diet and treated with normal saline. Systolic arterial pressure was measured by tail-cuff plethysmography. The left ventricular weight and left ventricular mass index were used to evaluate the ventricular hypertrophy. At the same time, we observed the changes of mRNA and protein of KLF4, endothelial nitric oxide synthase (eNOS), plasminogen activator inhibitor-1 (PAI-1), matrix metalloproteinase inhibitor-1 (TIMP-1) and collagen type Ⅳ in the myocardial tissue. Results The blood pressure, left ventricular mass (LVW) and left ventricular mass index (LVW/BW) of SHR rats increased significantly comparing with WKY rats, telmisartan can significantly reduce blood pressure, LVW and LVW/BW. The mRNA and protein levels of KLF4 and eNOS of SHR rats decreased significantly than that in WKY rats, while telmisartan increased their level. The mRNA and protein level of PAI-1, TIMP-1 and Collagen type Ⅳ of SHR rats increased significantly than that in WKY rats, whereas telmisartan eliminated these effect. Overexpression KLF4 in endothelial cell can reverse the effect of AngⅡ. Conclusions KLF4 plays an important role in the process of myocardial fibrosis, telmisartan treatment can significantly slow or reverse the pathological process through KLF4. Key words: Telmisartan; Hypertension; Fibrosis; Kruppel-like factor 4