(-)-Epigallocatechin-3-gallate, the major green tea catechin, regulates the desensitization of β1 adrenoceptor via GRK2 in experimental heart failure.

OBJECTIVE:We investigated the effect of (-)-epigallocatechin-3-gallate (EGCG) on cardiac function and its mechanism, which focused on the desensitization of β1-AR and GRK2 in heart failure (HF) rats. METHODS:HF was induced by abdominal aortic coarctation. Four weeks after HF induction, the rats were given EGCG (25, 50, 100 mg/kg/day). Cardiac function was assessed by measuring haemodynamic parameters. Histological changes were analyzed by HE and Masson's trichrome staining. The expression of β1-AR was detected by immunohistochemistry and immunofluorescence. The membrane expression of β1-AR and GRK2 was detected by western blot. The expression levels of β1-AR mRNA and GRK2 mRNA were evaluated by Q-PCR. RESULT:Compared to the control group, the left ventricular end diastolic pressure, mean blood pressure, heart weight/body weight, and posterior wall thickness in the HF group were significantly increased, whereas the left ventricular systolic pressure, maximum rate of left ventricular pressure rise (+ dP/dt _max) and maximum rate of left ventricular pressure fall (- dP/dt _max) were clearly decreased. EGCG could improve cardiac function by regulating these parameters. Inflammatory cell infiltration, irregularly arranged cardiomyocytes, swelling of cardiomyocytes and myocardial fibrosis were observed in HF rats' myocardial morphology, and EGCG obviously improved the morphological signs. The expression of β1-AR was significantly decreased in the left ventricle tissue of HF rats by immunohistochemistry and immunofluorescence. The membrane expression of β1-AR decreased, whereas GRK2 increased in vivo and in vitro by western blot. EGCG could down-regulate the membrane expression of GRK2 and up-regulate the expression of β1-AR. There were no significant differences in the total expression of β1-AR mRNA and GRK2 mRNA. CONCLUSIONS:EGCG has therapeutic effects on the heart function of HF rats. The mechanism might be related to the inhibition of the transfer membrane of GRK2 and to the reduction of the desensitization of β1-AR.

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