Effect of resveratrol on aniogtensin Ⅱ induced cardiomyocytes hypertrophy and FoxO1/MnSOD signaling pathway
10.3760/cma.j.issn.0253-3758.2015.08.015
- VernacularTitle:白藜芦醇对血管紧张素Ⅱ诱导的心肌细胞肥大及FoxO1/MnSOD信号通路的影响
- Author:
Xiaoyuan SUN
1
;
Xinzhong HUANG
Author Information
1. 213100,常州市武进中医院心内科
- Keywords:
Myocytes,cardiac;
Hypertrophy;
Angiotensin Ⅱ;
Resveratrol
- From:
Chinese Journal of Cardiology
2015;43(8):718-723
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect of resveratrol (RSV) on angiotensin Ⅱ (Ang Ⅱ) induced cardiomyocytes hypertrophy and FoxO1/MnSOD signaling pathway.Methods The cardiomyocytes isolated from neonatal Wistar rats were cultured with pancreatin and preplating technique and divided into five groups:control (CON),Ang Ⅱ (1 × 10-6 mol/L,AngⅡ),Ang Ⅱ +RSV (10 μmol/L),Ang Ⅱ + RSV (25 μmol/L),and Ang Ⅱ + RSV (50 μmol/L).3H-Leucine incorporation method were used to determine the cardiomyocyte protein synthesis rate.Cell size was measured by phase contrast microscope.The gene expression of A type natriuretic factor (ANF) was detected by real-time PCR.Western blot was used to measure the expression of MnSOD,FoxO1 and acety-FoxO1.Immunoprecipitation was used to detect the interaction between Sirt1 and FoxO1.Results Cardiomyocyte protein synthesis rate in Ang ⅡⅡ group was significantly higher in Ang Ⅱ group than in the control group ((1 971 ± 175) cpm vs.(1 216 ± 136) cpm,P ＜ 0.05),which could be significantly attenuated by RSV (10 μmol/L,25 μmol/L,50 μmol/L,all P＜0.05),especially in Ang Ⅱ +RSV (25 μmol/L) group((1 374 ±143) cpm).Cardiomyocytes size in Ang Ⅱ group was significantly larger than control group ((29.3 ± 3.2) μm vs.(19.4 ± 1.8) μm,P ＜ 0.05),which could be significantly reduced by cotreatment with RSV (10 μmol/L,25 μmol/L,50 μmol/L,all P ＜ 0.05),especially in Ang Ⅱ + RSV (25 μmol/L) group ((20.8 ± 2.1) μm).Ang Ⅱ also significantly upregulated ANP mRNA expression of cardiomyocytes (4.4 ± 0.4 vs.1.0 ± 0.1 in control group,P ＜ 0.05),which could be significantly inhibited by cotreatment with RSV,especially in Ang Ⅱ + RSV (25 μmol/L) group (2.2 ± 0.2).Ang Ⅱ significantly decreased MnSOD expression of cardiomyocytes compared with control group (P ＜ 0.05),which was reversed by RSV (25 μmol/L).The binding level of Sirt1 and FoxO1 was significantly lower (1.00 ±0.11 vs.1.63 ±0.16,P ＜0.05),and the expression of acetylation of FoxO1 was significantly higher in Ang Ⅱ group than in control group (1.48 ± 0.16 vs.1.00 ± 0.13,P ＜ 0.05),which was significantly reversed by cotreatment with RSV (25 μmol/L).Conclusions Resveratrol treatment can inhibit Ang Ⅱ induced cardiomyocyte hypertrophy.This protective effect is associated with reduced FoxO1 acetylation and activation of Sirt1,suggesting that Sirt1 may serve as a potential therapeutic target of cardiomyocyte hypertrophy.
