Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
Mol Med Rep. 2018 Apr;17(4):5074-5080. doi: 10.3892/mmr.2018.8496. Epub 2018 Jan 25.
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.
炎症在心肌梗死后（MI）驱动交感神经重塑中起着关键作用，激活素 A 已被认为是 MI 后炎症反应的重要介质。然而，激活素 A 是否影响 MI 后交感神经重塑仍不清楚。在本研究中，作者评估了激活素 A 在 MI 大鼠模型中对交感神经重塑的影响。大鼠随机分为假手术组、MI 组和 MI+卵泡抑素 300（FS，激活素 A 抑制剂）组。MI 后 4 周，通过 Western blot 和免疫组织化学方法评估心肌梗死后peri-infarct 区大鼠交感神经重塑和炎症因子的表达。通过超声心动图评估心脏功能。结果表明，FS 给药可显著降低 MI 后激活素 A、神经生长因子蛋白水平以及交感神经重塑标志物神经纤维中神经纤维阳性和蛋白表达的密度，包括生长相关蛋白 43 和酪氨酸羟化酶。此外，抑制激活素 A 可减少 MI 后心脏炎症，具体表现为：i）白细胞介素-1 和肿瘤坏死因子-α 蛋白表达减少；ii）浸润巨噬细胞和肌成纤维细胞的数量和/或比例面积减少；iii）磷酸化 p65 和 IκBα 水平降低。此外，激活素 A 抑制减轻 MI 后心脏功能障碍。这些结果表明，激活素 A 抑制通过抑制炎症反应减少 MI 后交感神经重塑。本研究表明激活素 A 可能是一种潜在的治疗靶点，可避免 MI 后交感神经重塑。
