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29.10.2019 | Original Article

Curcumin Induces Endothelium-Dependent Relaxation by Activating Endothelial TRPV4 Channels

Zeitschrift:
Journal of Cardiovascular Translational Research
Autoren:
Jing Shao, Jing Han, Yifei Zhu, Aiqin Mao, Zhiwei Wang, Ka Zhang, Xiaodong Zhang, Yufeng Zhang, Chunlei Tang, Xin Ma
Wichtige Hinweise
Associate Editor Junjie Xiao oversaw the review of this article
Jing Shao, Jing Han and Yifei Zhu contributed equally to this work.

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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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