RT Journal Article
T1 Protective Effects of Short-Chain Fatty Acids on Endothelial Dysfunction Induced by Angiotensin II.
A1 Robles-Vera, Iñaki
A1 Toral, Marta
A1 de la Visitación, Néstor
A1 Aguilera-Sánchez, Nazaret
A1 Redondo, Juan Miguel
A1 Duarte, Juan
K1 angiotensin II
K1 endothelial dysfunction
K1 nitric oxide
K1 oxidative stress
K1 short-chain fatty acids
AB 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 Ser239; 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 pSer239-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.
SN 1664-042X
YR 2020
FD 2020-04-16
LK https://hdl.handle.net/10668/27990
UL https://hdl.handle.net/10668/27990
LA en
DS RISalud
RD Apr 5, 2025