The Effect Of Carvedilol On Cardiac Fibroblasts Proliferation Induced By Angiotensin â…¡ In Vitro

Neuraoendocrine suppression therapy of heart failure had achieved significant success during the past few decades. The cumulative mortality of heart failure has been decreased by 30 ~ 40 % , contributes to the combining use of ACEI, ARB, ALD antagonists andβreceptor blockers. However, further inhibition of neuroendocrine factors and cardiac remodeling seem to have achieved a terminus. In recent years, the exploring of new therapeutic targets of heart failure has become one of the hottest topics. PKC is an important signal transduction molecule, which plays a great important role in the regulation of physiological functions, and has been considered to be relevant to a variety of heart diseases. However, the functions of PKC isforms during cardiac remodeling is not yet clear. The further detection of PKC can be expected to leading us to the new therapic target and mechanism in myocardial remodeling.Objective: To explore the effect of carvedilol on the fibroblast proliferation and expression of PKCαinduced by AngⅡin vitro.Materials and Methods: 10-7 mmol/L AngⅡwere used to induce the neonatal rat cardiac fibroblasts proliaferation. The cells were designed into 6 groups according to different processing factors : 1) Control group: serum-containing IMDM medium. 2) Model group: medium contains 10-7mmol /L AngⅡ. 3) Car1 group: medium contains 10-7mmol/L AngⅡand 10-5mmol / L carvedilol. 4) Car2 groups: medium contains10-7mmol/L AngⅡand 10-6mmol / L carvedilol. 5) Car3 groups: medium contains10-7 AngⅡand 10-7mmol / L carvedilol. 6) Car4 group: medium contains 10-7 AngⅡand 10-8mmol / L carvedilol. Groups were cultured in serum free medium for 12 hours before given different treatment factors respectively, and cultured for 24 to 48 hours according to the experimental needs. Cell proliferation rate were tested by MTT assay, the content of collagen were tested by hydroxyproline kit, and the expression of p-PKCαwere analyzed by Immunohistochemistry and Western blot.Results: The cell proliferation and the collagen synthesis were increased in the model group ,which cultured in medium with 10-7mmol / L AngⅡfor 48 hours, according to MTT assays and hydroxyproline kit compared with the control group(p<0.01). The expression of p-PKCαdetected by Immunohistochemistry and Western blot were increased in the model group which is cultured in medium with10-7mmol/L AngⅡfor 24 hours, compared with the control group(p <0.01 ). The effects above can be inhibit by 10-5 ~ 10-8mmol / l Carvedilol (p <0.05 or p <0.01). Conclusion: Carvedilol inhibits AngⅡ-induced cardiac fibroblast proliferation and collagen synthesis. Its mechanism might be relevant to inhibiting the expression of p-PKCα.