Activin A inhibition attenuates sympathetic neural remodeling following myocardial infarction in rats.
Mol Med Rep
; 17(4): 5074-5080, 2018 04.
Article
em En
| MEDLINE
| ID: mdl-29393433
ABSTRACT
Inflammation serves a critical role in driving sympathetic neural remodeling following myocardial infarction (MI), and activin A has been implicated as an important mediator of the inflammatory response postMI. However, whether activin A impacts sympathetic neural remodeling postMI remains unclear. In the present study, the authors assessed the effects of activin A on sympathetic neural remodeling in a rat model of MI. Rats were randomly divided into sham, MI, and MI + follistatin300 (FS, activin A inhibitor) groups. Cardiac tissues from the periinfarct zone were assessed for expression of sympathetic neural remodeling and inflammatory factors in rats 4 weeks postMI by western blotting and immunohistochemical methods. Heart function was assessed by echocardiography. It is demonstrated that FS administration significantly reduced postMI upregulation of activin A, nerve growth factor protein lever, and the density of nerve fibers with positive and protein expression of sympathetic neural remodeling markers in nerve fibers, which included growth associated protein 43 and tyrosine hydroxylase. In addition, inhibition of activin A reduced cardiac inflammation postMI based on the reduction of i) interleukin1 and tumor necrosis factorα protein expression, ii) numbers and/or proportional area of infiltrating macrophages and myofibroblasts and iii) phosphorylated levels of p65 and IκBα. Furthermore, activin A inhibition lessened heart dysfunction postMI. These results suggested that activin A inhibition reduced sympathetic neural remodeling postMI in part through inhibition of the inflammatory response. The current study implicates activin A as a potential therapeutic target to circumvent sympathetic neural remodeling post-MI.
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Base de dados:
MEDLINE
Assunto principal:
Sistema Nervoso Simpático
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Remodelação Ventricular
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Ativinas
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article