In:
Journal of Translational Medicine, Springer Science and Business Media LLC, Vol. 11, No. 1 ( 2013-12)
Abstract:
M 3 muscarinic acetylcholine receptor (M 3 -mAChR) is stably expressed in the myocardium, but its pathophysiological role remains largely undefined. This study aimed to investigate the role of M 3 -mAChR in cardiac hypertrophy induced by angiotensin II (Ang II) and elucidate the underlying mechanisms. Methods Cardiac-specific M 3 -mAChR overexpression transgenic (TG) mice and rat H9c2 cardiomyoblasts with ectopic expression of M 3 -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 M 3 -mAChR was upregulated in hypertrophic heart, while M 2 -mAChR expression did not change significantly. M 3 -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, M 3 -mAChR overexpression downregulated AT 1 receptor expression and inhibited the activation of MAPK signaling in the heart. Conclusion The upregulation of M 3 -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 AT 1 receptor.
Type of Medium:
Online Resource
ISSN:
1479-5876
DOI:
10.1186/1479-5876-11-209
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2013
detail.hit.zdb_id:
2118570-0
