Upregulation of M3 muscarinic receptor inhibits cardiac hypertrophy induced by angiotensin II
- Equal contributors
1 Department of Pharmacology (State-Province key lab of China), Harbin Medical University, Heilongjiang 150081, China
2 Department of Cardiac Care Unit, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China
3 Institute of Clinical Pharmacology of the Second Hospital, Harbin Medical University, Heilongjiang 150081, China
4 Department of Microbiology, Harbin, Heilongjiang, 150081 P. R. China
5 Department of Biochemistry, Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China
Journal of Translational Medicine 2013, 11:209 doi:10.1186/1479-5876-11-209Published: 12 September 2013
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.
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.
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.
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.