期刊
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
卷 25, 期 6, 页码 3136-3148出版社
WILEY
DOI: 10.1111/jcmm.16304
关键词
angiotensin II; fibrosis; hypertrophy; oxidative stress; scoparone
资金
- Shandong Natural Science Foundation [ZR2020QH336, ZR2016HB01]
- China Postdoctoral Science Foundation [2019M652399]
- State Key Program of the National Natural Science Foundation of China [82030059]
- National Natural Science Foundation of China [81600302, 81772036, 82072144, 81671952, 81873950, 81873953]
- Academic promotion programme of Shandong First Medical University [2019QL001]
- National Key R&D Program of China [2020YFC1512700, 2020YFC1512705, 2020YFC1512703, 2020YFC0846600]
- National S&T Fundamental Resources Investigation Project [2018FY100600, 2018FY100602]
- Taishan Pandeng Scholar Program of Shandong Province [tspd20181220]
- Taishan Young Scholar Program of Shandong Province [tsqn20161065, tsqn201812129]
- Youth Top-Talent Project of National Ten Thousand Talents Plan
- Qilu Young Scholar Program
- Fundamental Research Funds of Shandong University [2018JC011]
Scoparone can alleviate Ang II-induced myocardial hypertrophy and fibrosis by inhibiting oxidative stress mediated by RAC1. It also blocks Ang II-induced cardiomyocyte hypertrophy and cardiac fibroblast collagen synthesis.
Long-term poorly controlled myocardial hypertrophy often leads to heart failure and sudden death. Activation of ras-related C3 botulinum toxin substrate 1 (RAC1) by angiotensin II (Ang II) plays a pivotal role in myocardial hypertrophy. Previous studies have demonstrated that scoparone (SCO) has beneficial effects on hypertension and extracellular matrix remodelling. However, the function of SCO on Ang II-mediated myocardial hypertrophy remains unknown. In our study, a mouse model of myocardial hypertrophy was established by Ang II infusion (2 mg/kg/day) for 4 weeks, and SCO (60 mg/kg bodyweight) was administered by gavage daily. In vitro experiments were also performed. Our results showed that SCO could alleviate Ang II infusion-induced cardiac hypertrophy and fibrosis in mice. In vitro, SCO treatment blocks Ang II-induced cardiomyocyte hypertrophy, cardiac fibroblast collagen synthesis and differentiation to myofibroblasts. Meanwhile, we found that SCO treatment blocked Ang II-induced oxidative stress in cardiomyocytes and cardiac fibroblasts by inhibiting RAC1-GTP and total RAC1 in vivo and in vitro. Furthermore, reactive oxygen species (ROS) burst by overexpression of RAC1 completely abolished SCO-mediated protection in cardiomyocytes and cardiac fibroblasts in vitro. In conclusion, SCO, an antioxidant, may attenuate Ang II-induced myocardial hypertrophy by suppressing of RAC1 mediated oxidative stress.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据