The role of KLF4 in vascular smooth muscle cells on cardiac remodeling in mice with hypertension
Objective To investigate the regulatory effect of vascular smooth muscle cell Krüppel like factor 4 (KLF4) on cardiac remodeling in mice with hypertension.Methods A mouse model of hypertension was established via subcutaneous infusion of angiotensin Ⅱ(Ang Ⅱ) by using implanted osmotic pumps for 28 days,with a dose of 1500 ng/(kg·min) .We constructed the tamoxifen-induced vascular smooth muscle cell Klf4 specific knockout (Klf4-SMKO) mice.Thirteen Klf4-SMKO and thirteen Klf4-flox wild-type male mice,aged 9-10 weeks,were randomly divided into four groups:wild-type control group (Klf4-flox mice with saline infusion,n=6),Klf4-knockout control group (Klf4-SMKO mice with saline,n=6),wild-type hypertension group (Klf4-flox mice with Ang Ⅱ infusion,n=7),and Klf4-knockout hypertension group(Klf4-SMKO mice with Ang Ⅱ,n=7).Blood pressure of mice in hypertension groups were measured at day-0,7,14,21,and 28,respectively.Cardiac function was assessed with echocardiography.The ratio of heart weight to body weight was calculated,and the cross-sectional area of cardiomyocytes and cardiac fibrosis were detected by wheat germ agglutinin and Sirius red staining.Results The blood pressure exhibited no difference between the Klf4-SMKO and Klf4-flox hypertension groups.Echocardiography showed that smooth muscle Klf4 specific knockout decreased the left ventricular mass in mice with hypertension.Furthermore,Klf4 knockout significantly attenuated hypertension-induced increase of heart weight,as well as cardiomyocyte hypertrophy and perivascular fibrosis.Conclusions KLF4 deficiency in vascular smooth muscle cells ameliorates hypertension-induced pathological cardiac remodeling in mice.
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