Genetic- and Diet-Induced ω-3 Fatty Acid Enrichment Enhances TRPV4-Mediated Vasodilation in Mice

Authors

Rebeca Caires
Tessa A C Garrud
Luis O Romero
Carlos Fernández-Peña
Valeria Vásquez
Jonathan H Jaggar
Julio F Cordero-Morales

Publication Date

9-6-2022

Journal

Cell Reports

Abstract

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.

Keywords

Animals, Caenorhabditis elegans, Diet, Endothelial Cells, Fatty Acids, Omega-3, Humans, Mice, TRPV Cation Channels, Vasodilation

Comments

Supplementary Materials

PMID: 36070688