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Specific α7 nicotinic acetylcholine receptor agonist ameliorates isoproterenol‐induced cardiac remodelling in mice through TGF ‐β1/Smad3 pathway
Author(s) -
Yang YongHua,
Fang HuanLe,
Zhao Ming,
Wei XiangLan,
Zhang Ning,
Wang Shun,
Lu Yi,
Yu XiaoJiang,
Sun Lei,
He Xi,
Li DongLing,
Liu JinJun,
Zang WeiJin
Publication year - 2017
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.12819
Subject(s) - cardiac fibrosis , medicine , agonist , fibrosis , cardiac function curve , ventricular remodeling , endocrinology , western blot , inflammation , chemistry , muscle hypertrophy , transforming growth factor , receptor , heart failure , biochemistry , gene
Summary It is well‐accepted that inflammation plays an important role in the development of cardiac remodelling and that therapeutic approaches targeting inflammation can inhibit cardiac remodelling. Although a large amount of evidence indicates that activation of α7 nicotinic acetylcholine receptor (α7n AC hR) causes an anti‐inflammatory effect, the role of α7n AC hR in cardiac remodelling and the underlying mechanism have not been established. To investigate the effect of the specific α7n AC hR agonist, PNU 282987, on cardiac remodelling induced by isoproterenol ( ISO 60 mg/kg per day) in mice, the cardiomyocyte cross‐sectional area ( CSA ) and collagen volume fraction were evaluated by hematoxylin and eosin ( HE ) and Masson staining, respectively. Cardiac function and ventricular wall thickness were measured by echocardiography. The protein expressions of collagen I, matrix metalloproteinase 9 ( MMP ‐9), transforming growth factor β1 ( TGF ‐β1), and Smad3 were analyzed by Western blot. ISO ‐induced cardiac hypertrophy, characterized by an increase in the heart weight/body weight ratio, CSA and ventricular wall thickness. Moreover, cardiac fibrosis indices, such as collagen volume fraction, MMP ‐9 and collagen I protein expression, were also increased by ISO . PNU282987 not only attenuated cardiac hypertrophy but also decreased the cardiac fibrosis induced by ISO . Furthermore, PNU282987 suppressed TGF ‐β1 protein expression and the phosphorylation of Smad3 induced by ISO . In conclusion, PNU282987 ameliorated the cardiac remodelling induced by ISO , which may be related to the TGF ‐β1/Smad3 pathway. These data imply that the α7n AC hR may represent a novel therapeutic target for cardiac remodelling in many cardiovascular diseases.