@misc{10481/87474,
year = {2018},
month = {5},
url = {https://hdl.handle.net/10481/87474},
abstract = {The aim is to analyze whether the probiotic Lactobacillus fermentum CECT5716 (LC40) can prevent endothelial dysfunction and hypertension induced by tacrolimus in mice.
Tacrolimus increases systolic blood pressure (SBP) and impairs endothelium-dependent relaxation to acetylcholine and these effects are partially prevented by LC40. Endothelial dysfunction induced by tacrolimus is related to both increased nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX2) and uncoupled endothelial nitric oxide synthase (eNOS)-driven superoxide production and Rho-kinase-mediated eNOS inhibition. LC40 treatment prevents all the aortic changes induced by tacrolimus. LC40 restores the imbalance between T-helper 17 (Th17)/regulatory T (Treg) cells induced by tacrolimus in mesenteric lymph nodes and the spleen. Tacrolimus-induced gut dysbiosis, that is, it decreases microbial diversity, increases the Firmicutes/Bacteroidetes (F/B) ratio and decreases acetate- and butyrate-producing bacteria, and these effects are prevented by LC40. Fecal microbiota transplantation (FMT) from LC40-treated mice to control mice prevents the increase in SBP and the impaired relaxation to acetylcholine induced by tacrolimus.
 LC40 treatment prevents hypertension and endothelial dysfunction induced by tacrolimus by inhibiting gut dysbiosis. These effects are associated with a reduction in vascular oxidative stress, mainly through NOX2 downregulation and prevention of eNOS uncoupling, and inflammation possibly because of decreased Th17 and increased Treg cells polarization in mesenteric lymph nodes.},
organization = {This work was supported by Grants from Comisión Interministerial de Ciencia y Tecnología, Ministerio de Economía y competitividad (SAF2014-55523-R, SAF2014-55399-R, SAF2010-22066-C02-01, and -02, AGL2015-67995-C3-3-R), Junta de Andalucía (Proyecto de excelencia P12-CTS-2722, AGR-6826, and CTS 164) with funds from the European Union, and by the Ministerio de Economia y Competitividad, Instituto de Salud Carlos III (RIC, RD12/0042/0011, CIBER-ehd, CIBER-CV), Spain. M.S. is a postdoctoral fellow of Junta de Andalucía, M.R. is a postdoctoral fellow of RIC, A.R.-N. and F.A. are postdoctoral fellows of University of Granada.},
publisher = {WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim},
keywords = {T cells},
keywords = {Endothelial dysfunction},
keywords = {Gut dysbiosis},
title = {Lactobacillus fermentum Improves Tacrolimus-Induced Hypertension by Restoring Vascular Redox State and Improving eNOS Coupling},
doi = {10.1002/mnfr.201800033},
author = {Toral Jiménez, Marta and Romero Pérez, Miguel and Rodríguez Nogales, Alba and Jiménez Moleón, Rosario and Robles Vera, Iñaki and Algieri, Francesca and Chueca-Portuna, Natalia and Sánchez, Manuel and Visitación Pastor, Néstor de la and Olivares, Mónica and García, Federico and Pérez-Vizcaíno, Francisco and Gálvez Peralta, Julio Juan and Duarte Pérez, Juan Manuel},
}