Upregulation of M3 muscarinic receptor inhibits cardiac hypertrophy induced by angiotensin II

Journal of Translational Medicine

Zhimin Du¹  Yanjie Lu²  Xu Gao³  Lihua Sun²  Rong Huo²  Lanlan Wei⁴  Yanan Jiang²  Pengzhou Hang¹  Hongmei Han²  Haoxin Song²  Chao Wang²  Shu Wang⁵  Yan Liu² 

[1] Institute of Clinical Pharmacology of the Second Hospital, Harbin Medical University, Heilongjiang 150081, China;Department of Pharmacology (State-Province key lab of China), Harbin Medical University, Heilongjiang 150081, China;Department of Biochemistry, Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China;Department of Microbiology, Harbin, Heilongjiang, 150081 P. R. China;Department of Cardiac Care Unit, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China

关键词: Choline;    Angiotensin II;    M₃ muscarinic acetylcholine receptor;    Cardiac hypertrophy;   

Others  :  826663
DOI  :  10.1186/1479-5876-11-209

 received in 2013-04-30, accepted in 2013-09-04,  发布年份 2013

【 摘 要 】

Background

M₃ muscarinic acetylcholine receptor (M₃-mAChR) is stably expressed in the myocardium, but its pathophysiological role remains largely undefined. This study aimed to investigate the role of M₃-mAChR in cardiac hypertrophy induced by angiotensin II (Ang II) and elucidate the underlying mechanisms.

Methods

Cardiac-specific M₃-mAChR overexpression transgenic (TG) mice and rat H9c2 cardiomyoblasts with ectopic expression of M₃-mAChR were established. Models of cardiac hypertrophy were induced by transverse aortic constriction (TAC) or Ang II infusion in the mice in vivo, and by isoproterenol (ISO) or Ang II treatment of H9c2 cells in vitro. Cardiac hypertrophy was evaluated by electrocardiography (ECG) measurement, hemodynamic measurement and histological analysis. mRNA and protein expression were detected by real-time RT-PCR and Western blot analysis.

Results

M₃-mAChR was upregulated in hypertrophic heart, while M₂-mAChR expression did not change significantly. M₃-mAChR overexpression significantly attenuated the increased expression of atrial natriuretic peptide and β-myosin heavy chain induced by Ang II both in vivo and in vitro. In addition, M₃-mAChR overexpression downregulated AT₁ receptor expression and inhibited the activation of MAPK signaling in the heart.

Conclusion

The upregulation of M₃-mAChR during myocardial hypertrophy could relieve the hypertrophic response provoked by Ang II, and the mechanism may involve the inhibition of MAPK signaling through the downregulation of AT₁ receptor.

【 授权许可】

   
2013 Liu et al.; licensee BioMed Central Ltd.

【 图 表 】

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