4.7 Article

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

期刊

ACTA PHARMACOLOGICA SINICA
卷 38, 期 10, 页码 1329-1339

出版社

ACTA PHARMACOLOGICA SINICA
DOI: 10.1038/aps.2017.18

关键词

curcumin; smooth muscle; vascular contractility; myocardin; caveolin-1; Notch1

资金

  1. National Natural Science Foundation of China [31371161, 81670268, 30971170, 30971267]
  2. Natural Science Foundation of Hunan Province [2016JJ3109]

向作者/读者索取更多资源

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, the contractile responses of the thoracic aorta to KCl 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 mu mol/L) for 4 d, which was accompanied by upregulated expression of SM marker contractile proteins SM22 alpha and SM alpha-actin. In cultured vascular smooth muscle cells (VSMCs), curcumin (10, 25, 50 mu mol/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 Notch1-inhibited myocardin expression. Knockdown of caveolin-1 or activation of Notch1 signaling with Jagged1 (2 mu g/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-1-mediated inhibition of Notch1 activation and Notch1-mediated repression of myocardin expression. This may represent a novel pathway, through which curcumin protects blood vessels via the beneficial regulation of SM contractility.

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