Ye Li, Xu Mengnan, Hu Min, Zhang Hai, Tan Xianming, Li Qing, Shen Bing, Huang Junhao
School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui 230032, China.
Guangdong Provincial Key Laboratory of Sports and Health Promotion, Scientific Research Center, Guangzhou Sport University, Guangzhou, Guangdong, China.
Biochem Biophys Res Commun. 2018 Jan 1;495(1):41-45. doi: 10.1016/j.bbrc.2017.10.160. Epub 2017 Oct 31.
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-permeable cation channels in vascular endothelial cells. In this study, we hypothesized that irisin may induce endothelium-dependent vasodilation by activating Ca influx into endothelial cells via TRPV4 channels. In primary cultured rat mesenteric artery endothelial cells, irisin caused an increase in [Ca] due to extracellular Ca influx rather than release from Ca stores. Moreover, irisin-induced increases in [Ca] 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 influx via TRPV4 channels in rat mesenteric arteries.
鸢尾素是一种运动诱导产生的肌动蛋白，可促使白色脂肪细胞转化为棕色脂肪细胞，促进线粒体生物合成和能量消耗。鸢尾素对包括人类在内的动物的内皮功能具有血管保护作用。鸢尾素信号通路缺陷会导致肥胖和糖尿病中的内皮功能障碍。然而，鸢尾素对内皮功能影响的潜在机制尚未阐明。瞬时受体电位香草酸亚型4（TRPV4）通道是血管内皮细胞中最重要的钙通透性阳离子通道之一。在本研究中，我们假设鸢尾素可能通过激活经由TRPV4通道的钙内流进入内皮细胞，从而诱导内皮依赖性血管舒张。在原代培养的大鼠肠系膜动脉内皮细胞中，鸢尾素由于细胞外钙内流而非钙库释放导致[Ca]增加。此外，TRPV4抑制剂完全消除了鸢尾素诱导的[Ca]增加。此外，鸢尾素诱导大鼠肠系膜动脉的内皮依赖性血管舒张。然而，鸢尾素对非内皮依赖性血管舒张没有影响。此外，在存在TRPV4抑制剂的情况下，鸢尾素诱导的血管舒张完全被消除，表明TRPV4通道参与内皮依赖性血管舒张。本研究提供了首个证据，即鸢尾素诱导的内皮依赖性血管舒张与通过TRPV4通道刺激大鼠肠系膜动脉细胞外钙内流有关。
