Activin A inhibition attenuates sympathetic neural remodeling following myocardial infarction in rats

Hu,Juan; Wang,Xi; Tang,Yan‑Hong; Shan,Ying‑Guang; Zou,Qiang; Wang,Zhi‑Qiang; Huang,Cong‑Xin

doi:10.3892/mmr.2018.8496

Activin A inhibition attenuates sympathetic neural remodeling following myocardial infarction in rats

Authors:
- Juan Hu
- Xi Wang
- Yan‑Hong Tang
- Ying‑Guang Shan
- Qiang Zou
- Zhi‑Qiang Wang
- Cong‑Xin Huang
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Affiliations: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China
Published online on: January 25, 2018 https://doi.org/10.3892/mmr.2018.8496
Pages: 5074-5080
Copyright: © Hu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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 post‑MI. However, whether activin A impacts sympathetic neural remodeling post‑MI 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 + follistatin‑300 (FS, activin A inhibitor) groups. Cardiac tissues from the peri‑infarct zone were assessed for expression of sympathetic neural remodeling and inflammatory factors in rats 4 weeks post‑MI by western blotting and immunohistochemical methods. Heart function was assessed by echocardiography. It is demonstrated that FS administration significantly reduced post‑MI 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 post‑MI based on the reduction of i) interleukin‑1 and tumor necrosis factor‑α 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 post‑MI. These results suggested that activin A inhibition reduced sympathetic neural remodeling post‑MI 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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