Genetic- and diet-induced ω-3 fatty acid enrichment enhances TRPV4-mediated vasodilation in mice.

Autor:	Caires R; Department of Physiology, College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA., Garrud TAC; Department of Physiology, College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA., Romero LO; Department of Physiology, College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA; Integrated Biomedical Sciences Graduate Program, College of Graduate Health Sciences, Memphis, TN 38163, USA., Fernández-Peña C; Department of Physiology, College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA., Vásquez V; Department of Physiology, College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA., Jaggar JH; Department of Physiology, College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA., Cordero-Morales JF; Department of Physiology, College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA. Electronic address: jcordero@uthsc.edu.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2022 Sep 06; Vol. 40 (10), pp. 111306.
DOI:	10.1016/j.celrep.2022.111306
Abstrakt:	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. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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