Erythropoietin inhibits angiotensin Ⅱ induced cardiomyocyte hypertrophy in vitro via activating PI3K/Akt-eNOS pathway
10.3760/cma.j.issn.0253-3758.2009.05.013
- VernacularTitle:促红细胞生成素对乳鼠心肌细胞肥大及P13K/Akt-eNOS信号转导通路的影响
- Author:
Yuan WEN
1
;
Fe-Xin MA
;
Xin-Fin ZHANG
;
Li-Feng HONG
;
Da-Ying FENG
;
Zhen-Hua LU
Author Information
1. 南昌大学附属第一医院
- Keywords:
Erythropoietin;
Signal transduction;
Angiotensin Ⅱ
- From:
Chinese Journal of Cardiology
2009;37(5):436-440
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the effect of erythropoietin (EPO) on angiotensin Ⅱ (Ang Ⅱ) induced neonatal rat cardiomyocyte hypertrophy and the association with PI3K/Akt-eNOS signaling pathway. Methods Cardiomyocytes were isolated from new-born Sprague-Dawley rats and stimulated by Ang Ⅱ in vitro. The cell surface area and mRNA expression of atrial natriuretic factor (ANF) of cardiomyocytes were determined in the presence and absence of various concentrations of EPO, phosphatidylinositol 3'-kinase (PI3K) inhibitor LY294002 and nitric oxide synthase (NOS) inhibitor L-NAME. Intracellular signal molecules, such as Akt, phosphorylated Akt, eNOS and phosphorylated eNOS protein expressions were detected by western blot. Nitric oxide (NO) level in the supernatant of cultured cardiomyocytes was assayed by NO assay kit. Results EPO (20 U/ml) significantly inhibited Ang Ⅱ induced cardiomyocyte hypertrophy as shown by decreased cell surface area and ANF mRNA expression (all P ＜0.05). EPO also activated Akt and enhanced the expression of eNOS and its phosphorylation (all P ＜ 0.05), increased the NO production (P ＜0.01). These effects could be partially abolished by cotreatment with LY294002 or L-NAME (all P ＜ 0.05). Conclusion EPO attenuates Ang Ⅱ induced cardiomyocytes hypertrophy via activating PI3K-Akt-eNOS pathway and promoting NO production.
