TRPV4 is involved in irisin-induced endothelium-dependent vasodilation

Journal Article · Mon Jan 15 04:00:00 EST 2018 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2017.10.160· OSTI ID:23134083

Ye, Li; Xu, Mengnan ^[1]; Hu, Min ^[2]; Zhang, Hai ^[3]; Tan, Xianming ^[2]; Li, Qing ^[4]; Shen, Bing ^[1]; Huang, Junhao ^[2]

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1. School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui 230032 (China)
2. Guangdong Provincial Key Laboratory of Sports and Health Promotion, Scientific Research Center, Guangzhou Sport University, Guangzhou, Guangdong (China)
3. Department of Physical Education, Guangdong University of Petrochemical Technology, Maoming, Guangdong (China)
4. Central Laboratory of Medical Research Center, Anhui Provincial Hospital, Hefei, Anhui 230001 (China)

Highlights: • Irisin caused an increase in [Ca{sup 2+}]{sub i} due to extracellular Ca{sup 2+} influx rather than Ca{sup 2+} release in endothelial cells. • Pretreatment with TRPV4 channel inhibitor completely abolished irisin-induced increases in [Ca{sup 2+}]{sub i}. • Irisin induced endothelium-dependent vasodilation, however, it had no effect on endothelium-independent vasodilation. • Pretreatment with TRPV4 channel inhibitor fully abrogated irisin-induced vasodilation. Irisin, an exercise-induced myokine, induces conversion of white into brown adipocytes, promoting mitochondrial biogenesis and energy expenditure. Irisin has a vascular protective effect on endothelial function in animals, including humans. Defects in irisin signaling pathways result in endothelial dysfunction in obesity and diabetes. However, the mechanisms underlying the effects of irisin on endothelial function have not been elucidated. Transient receptor potential vanilloid subtype 4 (TRPV4) channels are one of the most important Ca{sup 2+}-permeable cation channels in vascular endothelial cells. In this study, we hypothesized that irisin may induce endothelium-dependent vasodilation by activating Ca{sup 2+} influx into endothelial cells via TRPV4 channels. In primary cultured rat mesenteric artery endothelial cells, irisin caused an increase in [Ca{sup 2+}]{sub i} due to extracellular Ca{sup 2+} influx rather than release from Ca{sup 2+} stores. Moreover, irisin-induced increases in [Ca{sup 2+}]{sub i} were completely abolished by a TRPV4 inhibitor. In addition, irisin induced endothelium-dependent vasodilation of rat mesenteric arteries. However, irisin had no effect on endothelium-independent vasodilation. Furthermore, irisin-induced vasodilation was fully abolished in the presence of a TRPV4 inhibitor, indicating the involvement of TRPV4 channels in endothelium-dependent vasodilation. This study provides the first evidence that irisin-induced endothelium-dependent vasodilation is related to the stimulation of extracellular Ca{sup 2+} influx via TRPV4 channels in rat mesenteric arteries.

• OSTI ID: 23134083
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 1 Vol. 495; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

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