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 x 10(-6) mol/L, Ang II), 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 II 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 I + 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.