Curcumin enhances vascular contractility via induction of myocardin in mouse smooth muscle cells  

作　　者：Shao-wei SUN Wen-juan TONG Zi-fen GUO Qin-hui TUO Xiao-yong LEI Cai-ping ZHANG Duan-fang LIAO Jian-xiong CHEN 

机构地区：[1]Institute of Pharmacy and Pharmacology, School of Life Science and Technology, University of South China, Hengyang 421001, China [2]Department of Gynecology and Obstetrics, First Affiliated Hospital, University of South China, Hengyang 421001, China [3]Medical School, Hunan University of Chinese Medicine, Changsha 410208, China [4]Department of Pharmacology and Toxicology, University of Mississippi Medical Center, School of Medicine, Jackson, MS, USA

出　　处：《Acta Pharmacologica Sinica》2017年第10期1329-1339,共11页中国药理学报（英文版）

摘　　要：A variety of cardiovascular diseases is accompanied by the loss of vascular contractility. This study sought to investigate the effects of curcumin, a natural polyphenolic compound present in turmeric, on mouse vascular contractility and the underlying mechanisms. After mice were administered curcumin （100 mg kg-1-d-1, ig） for 6 weeks, thecontractile responses of the thoracic aorta to KCI and phenylephrine were significantly enhanced compared with the control group. Furthermore, the contractility of vascular smooth muscle （SM） was significantly enhanced after incubation in curcumin （25 μmol/L） for 4 d, which was accompanied by upregulated expression of SM marker contractile proteins SM22a and SM a-actin, in cultured vascular smooth muscle cells （VSMCs）, curcumin （10, 25, 50 μmol/L） significantly increased the expression of myocardin, a ＂master regulator＂ of SM gene expression. Curcumin treatment also significantly increased the levels of caveolin-1 in VSMCs. We found that as a result of the upregulation of caveolin-1, curcumin blocked the activation of Notch1 and thereby abolished Notchl-inhibited myocardin expression. Knockdown of caveolin-1 or activation of Notch1 signaling with Jaggedl （2 pg/mL） diminished these effects of curcumin in VSMCs. These findings suggest that curcumin induces the expression of myocardin in mouse smooth muscle cells via a variety of mechanisms, including caveolin-l-mediated inhibition of Notch1 activation and Notchl-mediated repression of myocardin expression. This may represent a novel pathway, through which curcumin protects blood vessels via the beneficial regulation of SM contractility.A variety of cardiovascular diseases is accompanied by the loss of vascular contractility. This study sought to investigate the effects of curcumin, a natural polyphenolic compound present in turmeric, on mouse vascular contractility and the underlying mechanisms. After mice were administered curcumin （100 mg kg-1-d-1, ig） for 6 weeks, thecontractile responses of the thoracic aorta to KCI and phenylephrine were significantly enhanced compared with the control group. Furthermore, the contractility of vascular smooth muscle （SM） was significantly enhanced after incubation in curcumin （25 μmol/L） for 4 d, which was accompanied by upregulated expression of SM marker contractile proteins SM22a and SM a-actin, in cultured vascular smooth muscle cells （VSMCs）, curcumin （10, 25, 50 μmol/L） significantly increased the expression of myocardin, a ＂master regulator＂ of SM gene expression. Curcumin treatment also significantly increased the levels of caveolin-1 in VSMCs. We found that as a result of the upregulation of caveolin-1, curcumin blocked the activation of Notch1 and thereby abolished Notchl-inhibited myocardin expression. Knockdown of caveolin-1 or activation of Notch1 signaling with Jaggedl （2 pg/mL） diminished these effects of curcumin in VSMCs. These findings suggest that curcumin induces the expression of myocardin in mouse smooth muscle cells via a variety of mechanisms, including caveolin-l-mediated inhibition of Notch1 activation and Notchl-mediated repression of myocardin expression. This may represent a novel pathway, through which curcumin protects blood vessels via the beneficial regulation of SM contractility.

关 键 词：CURCUMIN smooth muscle vascular contractility MYOCARDIN caveolin-l NOTCHL 

分 类 号：Q463[生物学—生理学] TS202.3[轻工技术与工程—食品科学]