Genetic- and diet-induced ω-3 fatty acid enrichment enhances TRPV4-mediated vasodilation in mice.
Genetic- and diet-induced ω-3 fatty acid enrichment enhances TRPV4-mediated vasodilation in mice.
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DOI：
10.1016/j.celrep.2022.111306
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发表时间：
2022-09-06
期刊：
影响因子：
8.8
通讯作者：
Cordero-Morales, Julio F.
中科院分区：
文献类型：
--
作者：
Caires, Rebeca;Garrud, Tessa A. C.;Romero, Luis O.;Fernandez-Pena, Carlos;Vasquez, Valeria;Jaggar, Jonathan H.;Cordero-Morales, Julio F.
内皮细胞中的 TRPV4 通道激活会导致血管舒张，而 TRPV4 活性受损则与血管功能障碍有关。增加 TRPV4 活性的策略可以增强血管舒张并改善血管疾病。在这里，我们发现补充二十碳五烯酸 (EPA)（一种已知对心血管有益的 ω-3 多不饱和脂肪酸）可增加人体各种血管床内皮细胞中的 TRPV4 活性。携带线虫 FAT-1 酶（可将 ω-6 转化为 ω-3 多不饱和脂肪酸）的小鼠表现出更高的 EPA 含量，并且肠系膜动脉中 TRPV4 介导的血管舒张功能增强。同样，喂食富含 EPA 饮食的小鼠以内皮细胞特异性方式表现出增强和延长的 TRPV4 依赖性血管舒张作用。我们还表明，补充 EPA 可减少 TRPV4 脱敏，从而有助于延长血管舒张时间。 TRPV4 N 末端正电荷的中和会削弱 EPA 对通道脱敏的作用。这些发现强调了控制脂肪酸含量以增强 TRPV4 介导的血管舒张的有益效果。 TRPV4 活性降低与血管功能障碍有关。众所周知，膳食中摄入鱼油中的 ω-3 脂肪酸对心血管有益。凯雷斯等人。研究表明，遗传或饮食中富含 ω-3 脂肪酸可增强内皮细胞中的 TRPV4 功能以及小鼠中 TRPV4 介导的血管舒张作用。
TRPV4 channel activation in endothelial cells leads to vasodilation, while impairment of TRPV4 activity is implicated in vascular dysfunction. Strategies that increase TRPV4 activity could enhance vasodilation and ameliorate vascular disorders. Here, we show that supplementation with eicosapentaenoic acid (EPA), an ω-3 polyunsaturated fatty acid known to have beneficial cardiovascular effects, increases TRPV4 activity in human endothelial cells of various vascular beds. Mice carrying the C. elegans FAT-1 enzyme, which converts ω-6 to ω-3 polyunsaturated fatty acids, display higher EPA content and increased TRPV4-mediated vasodilation in mesenteric arteries. Likewise, mice fed an EPA-enriched diet exhibit enhanced and prolonged TRPV4-dependent vasodilation in an endothelial cell-specific manner. We also show that EPA supplementation reduces TRPV4 desensitization, which contributes to the prolonged vasodilation. Neutralization of positive charges in the TRPV4 N terminus impairs the effect of EPA on channel desensitization. These findings highlight the beneficial effects of manipulating fatty acid content to enhance TRPV4-mediated vasodilation. Reduced TRPV4 activity is associated with vascular dysfunction. Dietary consumption of ω-3 fatty acids, present in fish oils, is known to have beneficial cardiovascular effects. Caires et al. show that genetic or dietary enrichment of an ω-3 fatty acid enhances TRPV4 function in endothelial cells and TRPV4-mediated vasodilation in mice.
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