Yifei Zhu1, Lei Wen2, Sheng Wang1, Ka Zhang1, Yue Cui1, Chi Zhang1, Lei Feng1, Fan Yu1, Yongquan Chen1, Ruxing Wang3, Xin Ma1. 1. Wuxi School of Medicine, Jiangnan University, Wuxi 214000, China. 2. The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230000, China. 3. Wuxi People's Hospital, Wuxi 214000, China.
Abstract
AIMS: Previous studies have shown the intake of omega-3 polyunsaturated fatty acids is associated with low rates of obesity and ischaemic pathologies. Omega-3 also have anti-inflammatory and plaque-stabilization effects and regulate vasodilation and constriction. However, there are few studies of the role of omega-3 in flow-induced vasodilation involving Ca2+-permeable ion channel TRPV4 in high-fat diet-induced obese (DIO) mouse. Here, we determined whether omega-3 protect against vascular dysfunction induced by a high-fat diet by enhancing TRPV4 activity and subsequently improving flow-mediated vasodilation. METHODS AND RESULTS: Flow-mediated vasodilation in second-order mesenteric arteries from mice was measured using a pressure myograph. The intracellular Ca2+ concentration in response to flow and GSK1016790A (a TRPV4 agonist) was measured by Fluo-4 fluorescence. Whole-cell current was measured by patch clamp. Cell membrane tether force was measured by atomic force microscopy. Impairment of flow-mediated vasodilation in arteries and Ca2+ influx in endothelial cells from DIO mice was restored by omega-3 treatment. The improved flow-induced vasodilation was inhibited by the TRPV4 antagonist HC067047 and in TRPV4-/- mice. Omega-3 treatment enhanced endothelial TRPV4 activity and altered cell membrane mechanic property, as indicated by enhanced GSK1016790A-induced Ca2+ influx and whole-cell current and altered membrane mean tether force in endothelial cells from DIO mice. CONCLUSION: Omega-3 improve vascular function by improving flow-induced vasodilation via enhancing TRPV4 activity in the endothelium of obese mice which may be related to improved cell membrane physical property. Activation of TRPV4 in endothelium plays an important role in the protective mechanisms of omega-3 against vascular dysfunction in obesity by improving flow-mediated vasodilation. Published on behalf of the European Society of Cardiology. All rights reserved.
AIMS: Previous studies have shown the intake of omega-3 polyunsaturated fatty acids is associated with low rates of obesity and ischaemic pathologies. Omega-3 also have anti-inflammatory and plaque-stabilization effects and regulate vasodilation and constriction. However, there are few studies of the role of omega-3 in flow-induced vasodilation involving Ca2+-permeable ion channel TRPV4 in high-fat diet-induced obese (DIO) mouse. Here, we determined whether omega-3 protect against vascular dysfunction induced by a high-fat diet by enhancing TRPV4 activity and subsequently improving flow-mediated vasodilation. METHODS AND RESULTS: Flow-mediated vasodilation in second-order mesenteric arteries from mice was measured using a pressure myograph. The intracellular Ca2+ concentration in response to flow and GSK1016790A (a TRPV4 agonist) was measured by Fluo-4 fluorescence. Whole-cell current was measured by patch clamp. Cell membrane tether force was measured by atomic force microscopy. Impairment of flow-mediated vasodilation in arteries and Ca2+ influx in endothelial cells from DIO mice was restored by omega-3 treatment. The improved flow-induced vasodilation was inhibited by the TRPV4 antagonist HC067047 and in TRPV4-/- mice. Omega-3 treatment enhanced endothelial TRPV4 activity and altered cell membrane mechanic property, as indicated by enhanced GSK1016790A-induced Ca2+ influx and whole-cell current and altered membrane mean tether force in endothelial cells from DIO mice. CONCLUSION: Omega-3 improve vascular function by improving flow-induced vasodilation via enhancing TRPV4 activity in the endothelium of obese mice which may be related to improved cell membrane physical property. Activation of TRPV4 in endothelium plays an important role in the protective mechanisms of omega-3 against vascular dysfunction in obesity by improving flow-mediated vasodilation. Published on behalf of the European Society of Cardiology. All rights reserved.
Authors: Mariely Mendes Furtado; Joana Érica Lima Rocha; Ana Victória da Silva Mendes; Renato Sampaio Mello Neto; Ana Karolinne da Silva Brito; José Otávio Carvalho Sena de Almeida; Emerson Iuri Rodrigues Queiroz; José Vinícius de Sousa França; Ana Lina de Carvalho Cunha Sales; Andreanne Gomes Vasconcelos; Wanessa Felix Cabral; Luana de Oliveira Lopes; Iolanda Souza do Carmo; Selma Aparecida Souza Kückelhaus; José Roberto de Souza de Almeida Leite; Adriana Maria Viana Nunes; Marcia Dos Santos Rizzo; Antônia Maria das Graças Lopes Citó; Ana Karina Marques Fortes Lustosa; Massimo Lucarini; Alessandra Durazzo; Maria do Carmo de Carvalho E Martins; Daniel Dias Rufino Arcanjo Journal: Biology (Basel) Date: 2022-01-27