Beneficial effects of muscone on cardiac remodeling in a mouse model of myocardial infarction

Wang,Xiaoyan; Meng,Haoyu; Chen,Pengsheng; Yang,Naiquan; Lu,Xin; Wang,Ze-Mu; Gao,Wei; Zhou,Ningtian; Zhang,Min; Xu,Zhihui; Chen,Bo; Tao,Zhengxian; Wang,Liangsheng; Yang,Zhijian; Zhu,Tiebin

doi:10.3892/ijmm.2014.1766

Beneficial effects of muscone on cardiac remodeling in a mouse model of myocardial infarction

Authors:
- Xiaoyan Wang
- Haoyu Meng
- Pengsheng Chen
- Naiquan Yang
- Xin Lu
- Ze-Mu Wang
- Wei Gao
- Ningtian Zhou
- Min Zhang
- Zhihui Xu
- Bo Chen
- Zhengxian Tao
- Liangsheng Wang
- Zhijian Yang
- Tiebin Zhu
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Affiliations: Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China, Department of Cardiology, Huai'an Second People's Hospital Affiliated to Xuzhou Medical College, Huai'an, Jiangsu 223002, P.R. China
Published online on: May 2, 2014 https://doi.org/10.3892/ijmm.2014.1766
Pages: 103-111
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Musk has been traditionally used in East Asia to alleviate the symptoms of angina pectoris. However, it remains unclear as to whether muscone, the main active ingredient of musk, has any beneficial effects on persistent myocardial ischemia in vivo. The aim of the present study was to investigate whether muscone can improve cardiac function and attenuate myocardial remodeling following myocardial infarction (MI) in mice. Mice were subjected to permanent ligation of the left anterior descending coronary artery to induce MI, and then randomly treated with muscone (2 mg/kg/day) or the vehicle (normal saline) for 3 weeks. Sham-operated mice were used as controls and were also administered the vehicle (normal saline). Treatment with muscone significantly improved cardiac function and exercise tolerance, as evidenced by the decrease in the left ventricular end-systolic diameter, left ventricular end-diastolic diameter, as well as an increase in the left ventricular ejection fraction, left ventricular fractional shortening and time to exhaustion during swimming. Pathological and morphological assessments indicated that treatment with muscone alleviated myocardial fibrosis, collagen deposition and improved the heart weight/body weight ratio. Muscone inhibited the inflammatory response by reducing the expression of transforming growth factor (TGF)‑β1, tumor necrosis factor (TNF)-α, interleukin (IL)-1β and nuclear factor (NF)-κB. Treatment with muscone also reduced myocardial apoptosis by enhancing Bcl-2 and suppressing Bax expression. Muscone also induced the phosphorylation of protein kinase B (Akt) and endothelial nitric oxide synthase (eNOS). Our results demonstrate that muscone ameliorates cardiac remodeling and dysfunction induced by MI by exerting anti-fibrotic, anti-inflammatory and anti-apoptotic effects in the ischemic myocardium.

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