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TRPC5 mediates endothelium-dependent contraction in the carotid artery of diet-induced obese mice

Abstract

Little is known about the contribution of the transient receptor potential canonical channel isoform 5 (TRPC5), a Ca2+-sensitive channel, to vasoconstriction in obesity. In this study, we found that the TRPC5 expression and carotid artery contraction of diet-induced obese (DIO) mice were significantly higher than those of wild-type mice. Endothelium-dependent vasocontraction was inhibited by the TRPC5 inhibitor clemizole and the knockout of TRPC5 in DIO mouse carotid arteries, while activation of TRPC5 enhanced contraction in wild-type mice. TRPC5-regulated vasocontraction can be inhibited by the ROS scavenger NAC and the COX-2 inhibitor NS-398. Our study suggested that upregulation of TRPC5 contributes to endothelium-dependent contraction, which is involved in ROS production and COX-2 expression in DIO mouse carotid arteries. From these results, we speculated that TRPC5 mediated endothelium-dependent contraction in the carotid artery of DIO mice, which was achieved by increasing the levels of ROS and COX-2 expression.

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Acknowledgements

We thank Professor David E. Clapham (Harvard Medical School, USA) for giving us the TRPC5-knockout (TRPC5-/-) mice as a gift. We appreciate Dr Chunlei Tang (Jiangnan University, China) for assistance with the preparation of the AM237 compound.

Funding

This work was supported by the National Natural Science Foundation of China (81622007, 81960662, 82000291, and 82025005), the Chang Jiang Scholars Program (Q2015106), the Fundamental Research Funds for the Central Universities (JUSRP51704A), the National First-Class Discipline Program of Food Science and Technology (JUFSTR20180101), the Fundamental Research Funds for Young Scholars of Jiangnan University (JUSRP12046), and the Natural Science Foundation for Young Scholars of Jiangsu Province (BK20190596).

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The experimental design and operation of this study were mainly completed by YC and SW. The paper was written by YC and SW. YZ and XM guided the overall idea of the study. FY and KZ put forward valuable opinions on the writing of the article. XM provided a critical reading of the manuscript.

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Correspondence to Xin Ma.

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Chu, Y., Wang, S., Zhu, Y. et al. TRPC5 mediates endothelium-dependent contraction in the carotid artery of diet-induced obese mice. Hypertens Res 45, 1945–1953 (2022). https://doi.org/10.1038/s41440-022-01017-9

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  • DOI: https://doi.org/10.1038/s41440-022-01017-9

Keywords

  • TRPC5
  • Diet-induced obesity
  • Endothelium-dependent contraction
  • Carotid artery

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