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Curcumin Induces Endothelium-Dependent Relaxation by Activating Endothelial TRPV4 Channels

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Abstract

It is well-known that curcumin, as a plant substance, has vascular protective effects. TRPV4 (transient receptor potential vanilloid 4) is a highly Ca2+-selective channel in vascular endothelium. In our study, fluorescent Ca2+ imaging in mesenteric arterial endothelial cells (MAECs) and overexpressed TRPV4 human embryonic kidney (HEK293) cells showed that curcumin dose-dependently stimulated Ca2+ influx. Whole-cell patch clamp proved that curcumin stimulated the TRPV4-mediated currents in TRPV4-HEK293 cells. The TRPV4-specific blocker HC067047 markedly decreased the whole-cell current. Molecular modeling and docking showed that the binding site of curcumin and TRPV4 was mainly in the amino acid sequence LYS340-LEU349 of TRPV4 protein. Furthermore, curcumin dose-dependently induced the endothelium-dependent vessel dilatation in small mesenteric arteries. Therefore, our results demonstrated that curcumin stimulates Ca2+ entry in endothelial cells and improves endothelium-dependent vessel relaxation by activating TRPV4 channels. Moreover, we identified the specific binding sites of curcumin and TRPV4, thereby highlighting its potential therapeutic target of cardiovascular diseases.

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Abbreviations

TRPV4:

Transient receptor potential vanilloid 4

WT:

Wild type

MAECs:

Mesenteric arterial endothelial cells

Cur:

Curcumin

TRPV4−/− :

TRPV4 knockout

Phe:

Phenylephrine

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Funding

This project was supported by the China National Natural Science Foundation (81622007, to Xin Ma). This project was also supported by the Chang Jiang Scholars Program (Q2015106, to Xin Ma).

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Author notes

  1. Jing Shao, Jing Han and Yifei Zhu contributed equally to this work.

Authors and Affiliations

  1. Wuxi School of Medicine, Jiangnan University, Wuxi, China

    Jing Shao, Jing Han, Yifei Zhu, Aiqin Mao, Zhiwei Wang, Ka Zhang, Xiaodong Zhang, Yufeng Zhang & Xin Ma

  2. School of Pharmaceutical Sciences, Jiangnan University, Wuxi, China

    Chunlei Tang

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  1. Jing Shao
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Correspondence to Xin Ma.

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The authors declare that they have no competing interests.

Ethical Approval

All animal experiments were conducted in compliance with the guidance of Animal Care and Use of Laboratory Animals published by the US National Institute of Health and with the approval of the Animal Experimentations Ethics Committee, Jiangnan University.

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Associate Editor Junjie Xiao oversaw the review of this article

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Shao, J., Han, J., Zhu, Y. et al. Curcumin Induces Endothelium-Dependent Relaxation by Activating Endothelial TRPV4 Channels. J. of Cardiovasc. Trans. Res. 12, 600–607 (2019). https://doi.org/10.1007/s12265-019-09928-8

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