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Serelaxin improves cardiac and renal function in DOCA-salt hypertensive rats

Serelaxin, a recombinant form of the naturally occurring peptide hormone relaxin-2, is a pleiotropic vasodilating hormone that has been studied in patients with acute heart failure. In this study, the effects of serelaxin on cardiac and renal function, fibrosis, inflammation and lipid accumulation w...

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Autores principales: Wang, Dong, Luo, Yuhuan, Myakala, Komuraiah, Orlicky, David J., Dobrinskikh, Evgenia, Wang, Xiaoxin, Levi, Moshe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5574886/
https://www.ncbi.nlm.nih.gov/pubmed/28851937
http://dx.doi.org/10.1038/s41598-017-09470-0
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author Wang, Dong
Luo, Yuhuan
Myakala, Komuraiah
Orlicky, David J.
Dobrinskikh, Evgenia
Wang, Xiaoxin
Levi, Moshe
author_facet Wang, Dong
Luo, Yuhuan
Myakala, Komuraiah
Orlicky, David J.
Dobrinskikh, Evgenia
Wang, Xiaoxin
Levi, Moshe
author_sort Wang, Dong
collection PubMed
description Serelaxin, a recombinant form of the naturally occurring peptide hormone relaxin-2, is a pleiotropic vasodilating hormone that has been studied in patients with acute heart failure. In this study, the effects of serelaxin on cardiac and renal function, fibrosis, inflammation and lipid accumulation were studied in DOCA-salt treated rats. Uninephrectomized rats were assigned to two groups: controls provided with normal drinking water and DOCA provided with DOCA pellets and sodium chloride drinking water. After 4 weeks, the DOCA-salt rats were randomly selected and implanted with osmotic minipumps delivering vehicle or serelaxin for another 4 weeks. Treatment with serelaxin prevented cardiac and renal dysfunction in DOCA-salt rats. Serelaxin prevented cardiac and renal fibrosis, as determined by Picrosirius Red staining and Second Harmonic Generation (SHG) Microscopy. Treatment of DOCA-salt rats with serelaxin decreased renal inflammation, including the expression of TGF-β, NFκB, MCP-1, IL-1, IL-6, ICAM-1, VCAM-1 and CD68 macrophages. Serelaxin also decreased lipid accumulation in kidney in part by decreasing SREBP-1c, SREBP-2, ChREBP, FATP1, HMGCoAR, and LDL receptor, and increasing Acox1 and ABCA1. In summary, serelaxin reversed DOCA-salt induced cardiac and renal dysfunction.
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spelling pubmed-55748862017-09-01 Serelaxin improves cardiac and renal function in DOCA-salt hypertensive rats Wang, Dong Luo, Yuhuan Myakala, Komuraiah Orlicky, David J. Dobrinskikh, Evgenia Wang, Xiaoxin Levi, Moshe Sci Rep Article Serelaxin, a recombinant form of the naturally occurring peptide hormone relaxin-2, is a pleiotropic vasodilating hormone that has been studied in patients with acute heart failure. In this study, the effects of serelaxin on cardiac and renal function, fibrosis, inflammation and lipid accumulation were studied in DOCA-salt treated rats. Uninephrectomized rats were assigned to two groups: controls provided with normal drinking water and DOCA provided with DOCA pellets and sodium chloride drinking water. After 4 weeks, the DOCA-salt rats were randomly selected and implanted with osmotic minipumps delivering vehicle or serelaxin for another 4 weeks. Treatment with serelaxin prevented cardiac and renal dysfunction in DOCA-salt rats. Serelaxin prevented cardiac and renal fibrosis, as determined by Picrosirius Red staining and Second Harmonic Generation (SHG) Microscopy. Treatment of DOCA-salt rats with serelaxin decreased renal inflammation, including the expression of TGF-β, NFκB, MCP-1, IL-1, IL-6, ICAM-1, VCAM-1 and CD68 macrophages. Serelaxin also decreased lipid accumulation in kidney in part by decreasing SREBP-1c, SREBP-2, ChREBP, FATP1, HMGCoAR, and LDL receptor, and increasing Acox1 and ABCA1. In summary, serelaxin reversed DOCA-salt induced cardiac and renal dysfunction. Nature Publishing Group UK 2017-08-29 /pmc/articles/PMC5574886/ /pubmed/28851937 http://dx.doi.org/10.1038/s41598-017-09470-0 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Wang, Dong
Luo, Yuhuan
Myakala, Komuraiah
Orlicky, David J.
Dobrinskikh, Evgenia
Wang, Xiaoxin
Levi, Moshe
Serelaxin improves cardiac and renal function in DOCA-salt hypertensive rats
title Serelaxin improves cardiac and renal function in DOCA-salt hypertensive rats
title_full Serelaxin improves cardiac and renal function in DOCA-salt hypertensive rats
title_fullStr Serelaxin improves cardiac and renal function in DOCA-salt hypertensive rats
title_full_unstemmed Serelaxin improves cardiac and renal function in DOCA-salt hypertensive rats
title_short Serelaxin improves cardiac and renal function in DOCA-salt hypertensive rats
title_sort serelaxin improves cardiac and renal function in doca-salt hypertensive rats
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5574886/
https://www.ncbi.nlm.nih.gov/pubmed/28851937
http://dx.doi.org/10.1038/s41598-017-09470-0
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