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Protective Effects of Short-Chain Fatty Acids on Endothelial Dysfunction Induced by Angiotensin II
Short-chain fatty acids (SCFAs) are among the main classes of bacterial metabolic products and are mainly synthesized in the colon through bacterial fermentation. Short-chain fatty acids, such as acetate, butyrate, and propionate, reduce endothelial activation induced by proinflammatory mediators, a...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7176911/ https://www.ncbi.nlm.nih.gov/pubmed/32372967 http://dx.doi.org/10.3389/fphys.2020.00277 |
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author | Robles-Vera, Iñaki Toral, Marta de la Visitación, Néstor Aguilera-Sánchez, Nazaret Redondo, Juan Miguel Duarte, Juan |
author_facet | Robles-Vera, Iñaki Toral, Marta de la Visitación, Néstor Aguilera-Sánchez, Nazaret Redondo, Juan Miguel Duarte, Juan |
author_sort | Robles-Vera, Iñaki |
collection | PubMed |
description | Short-chain fatty acids (SCFAs) are among the main classes of bacterial metabolic products and are mainly synthesized in the colon through bacterial fermentation. Short-chain fatty acids, such as acetate, butyrate, and propionate, reduce endothelial activation induced by proinflammatory mediators, at least in part, by activation of G protein–coupled receptors (GPRs): GPR41 and GPR43. The objective of the study was to analyze the possible protective effects of SCFAs on endothelial dysfunction induced by angiotensin II (AngII). Rat aortic endothelial cells (RAECs) and rat aortas were incubated with AngII (1 μM) for 6 h in the presence or absence of SCFAs (5–10 mM). In RAECs, we found that AngII reduces the production of nitric oxide (NO) stimulated by calcium ionophore A23187; increases the production of reactive oxygen species (ROS), both from the nicotinamide adenine dinucleotide phosphate oxidase system and the mitochondria; diminishes vasodilator-stimulated phosphoprotein (VASP) phosphorylation at Ser(239); reduces GPR41 and GPR43 mRNA level; and reduces the endothelium-dependent relaxant response to acetylcholine in aorta. Coincubation with butyrate and acetate, but not with propionate, increases both NO production and pSer(239)-VASP, reduces the concentration of intracellular ROS, and improves relaxation to acetylcholine. The beneficial effects of butyrate were inhibited by the GPR41 receptor antagonist, β-hydroxybutyrate, and by the GPR43 receptor antagonist, GLPG0794. Butyrate inhibited the down-regulation of GPR41 and GPR43 induced by AngII, being without effect acetate and propionate. Neither β-hydroxybutyrate nor GLPG0794 affects the protective effect of acetate in endothelial dysfunction. In conclusion, acetate and butyrate improve endothelial dysfunction induced by AngII by increasing the bioavailability of NO. The effect of butyrate seems to be related to GPR41/43 activation, whereas acetate effects were independent of GPR41/43. |
format | Online Article Text |
id | pubmed-7176911 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-71769112020-05-05 Protective Effects of Short-Chain Fatty Acids on Endothelial Dysfunction Induced by Angiotensin II Robles-Vera, Iñaki Toral, Marta de la Visitación, Néstor Aguilera-Sánchez, Nazaret Redondo, Juan Miguel Duarte, Juan Front Physiol Physiology Short-chain fatty acids (SCFAs) are among the main classes of bacterial metabolic products and are mainly synthesized in the colon through bacterial fermentation. Short-chain fatty acids, such as acetate, butyrate, and propionate, reduce endothelial activation induced by proinflammatory mediators, at least in part, by activation of G protein–coupled receptors (GPRs): GPR41 and GPR43. The objective of the study was to analyze the possible protective effects of SCFAs on endothelial dysfunction induced by angiotensin II (AngII). Rat aortic endothelial cells (RAECs) and rat aortas were incubated with AngII (1 μM) for 6 h in the presence or absence of SCFAs (5–10 mM). In RAECs, we found that AngII reduces the production of nitric oxide (NO) stimulated by calcium ionophore A23187; increases the production of reactive oxygen species (ROS), both from the nicotinamide adenine dinucleotide phosphate oxidase system and the mitochondria; diminishes vasodilator-stimulated phosphoprotein (VASP) phosphorylation at Ser(239); reduces GPR41 and GPR43 mRNA level; and reduces the endothelium-dependent relaxant response to acetylcholine in aorta. Coincubation with butyrate and acetate, but not with propionate, increases both NO production and pSer(239)-VASP, reduces the concentration of intracellular ROS, and improves relaxation to acetylcholine. The beneficial effects of butyrate were inhibited by the GPR41 receptor antagonist, β-hydroxybutyrate, and by the GPR43 receptor antagonist, GLPG0794. Butyrate inhibited the down-regulation of GPR41 and GPR43 induced by AngII, being without effect acetate and propionate. Neither β-hydroxybutyrate nor GLPG0794 affects the protective effect of acetate in endothelial dysfunction. In conclusion, acetate and butyrate improve endothelial dysfunction induced by AngII by increasing the bioavailability of NO. The effect of butyrate seems to be related to GPR41/43 activation, whereas acetate effects were independent of GPR41/43. Frontiers Media S.A. 2020-04-16 /pmc/articles/PMC7176911/ /pubmed/32372967 http://dx.doi.org/10.3389/fphys.2020.00277 Text en Copyright © 2020 Robles-Vera, Toral, de la Visitación, Aguilera-Sánchez, Redondo and Duarte. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Physiology Robles-Vera, Iñaki Toral, Marta de la Visitación, Néstor Aguilera-Sánchez, Nazaret Redondo, Juan Miguel Duarte, Juan Protective Effects of Short-Chain Fatty Acids on Endothelial Dysfunction Induced by Angiotensin II |
title | Protective Effects of Short-Chain Fatty Acids on Endothelial Dysfunction Induced by Angiotensin II |
title_full | Protective Effects of Short-Chain Fatty Acids on Endothelial Dysfunction Induced by Angiotensin II |
title_fullStr | Protective Effects of Short-Chain Fatty Acids on Endothelial Dysfunction Induced by Angiotensin II |
title_full_unstemmed | Protective Effects of Short-Chain Fatty Acids on Endothelial Dysfunction Induced by Angiotensin II |
title_short | Protective Effects of Short-Chain Fatty Acids on Endothelial Dysfunction Induced by Angiotensin II |
title_sort | protective effects of short-chain fatty acids on endothelial dysfunction induced by angiotensin ii |
topic | Physiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7176911/ https://www.ncbi.nlm.nih.gov/pubmed/32372967 http://dx.doi.org/10.3389/fphys.2020.00277 |
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