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Reduced Cystathionine γ-Lyase and Increased miR-21 Expression Are Associated with Increased Vascular Resistance in Growth-Restricted Pregnancies: Hydrogen Sulfide as a Placental Vasodilator
Increased vascular impedance in the fetoplacental circulation is associated with fetal hypoxia and growth restriction. We sought to investigate the role of hydrogen sulfide (H(2)S) in regulating vasomotor tone in the fetoplacental vasculature. H(2)S is produced endogenously by catalytic activity of...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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American Society for Investigative Pathology
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3608014/ https://www.ncbi.nlm.nih.gov/pubmed/23410520 http://dx.doi.org/10.1016/j.ajpath.2013.01.001 |
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author | Cindrova-Davies, Tereza Herrera, Emilio A. Niu, Youguo Kingdom, John Giussani, Dino A. Burton, Graham J. |
author_facet | Cindrova-Davies, Tereza Herrera, Emilio A. Niu, Youguo Kingdom, John Giussani, Dino A. Burton, Graham J. |
author_sort | Cindrova-Davies, Tereza |
collection | PubMed |
description | Increased vascular impedance in the fetoplacental circulation is associated with fetal hypoxia and growth restriction. We sought to investigate the role of hydrogen sulfide (H(2)S) in regulating vasomotor tone in the fetoplacental vasculature. H(2)S is produced endogenously by catalytic activity of cystathionine β-synthase and cystathionine γ-lyase (CSE). Immunohistochemical analysis localized CSE to smooth muscle cells encircling arteries in stem villi. Immunoreactivity was reduced in placentas from pregnancies with severe early-onset growth-restriction and preeclampsia displaying abnormal umbilical artery Doppler waveforms compared with preeclamptic placentas with normal waveforms and controls. These findings were confirmed at the protein and mRNA levels. MicroRNA-21, which negatively regulates CSE expression, was increased in placentas with abnormal Doppler waveforms. Exposure of villus explants to hypoxia-reoxygenation significantly reduced CSE protein and mRNA and increased microRNA-21 expression. No changes were observed in cystathionine β-synthase expression, immunolocalized principally to the trophoblast, in pathologic placentas or in vitro. Finally, perfusion of normal placentas with an H(2)S donor, after preconstriction with a thromboxane mimetic, resulted in dose-dependent vasorelaxation. Glibenclamide and N(G)-nitro-l-arginine methyl ester partially blocked the effect, indicating that H(2)S acts through ATP-sensitive K(+) channels and nitric oxide synthesis. These results demonstrate that H(2)S is a powerful vasodilator of the placental vasculature and that expression of CSE is reduced in placentas associated with increased vascular resistance. |
format | Online Article Text |
id | pubmed-3608014 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | American Society for Investigative Pathology |
record_format | MEDLINE/PubMed |
spelling | pubmed-36080142013-04-05 Reduced Cystathionine γ-Lyase and Increased miR-21 Expression Are Associated with Increased Vascular Resistance in Growth-Restricted Pregnancies: Hydrogen Sulfide as a Placental Vasodilator Cindrova-Davies, Tereza Herrera, Emilio A. Niu, Youguo Kingdom, John Giussani, Dino A. Burton, Graham J. Am J Pathol Regular Article Increased vascular impedance in the fetoplacental circulation is associated with fetal hypoxia and growth restriction. We sought to investigate the role of hydrogen sulfide (H(2)S) in regulating vasomotor tone in the fetoplacental vasculature. H(2)S is produced endogenously by catalytic activity of cystathionine β-synthase and cystathionine γ-lyase (CSE). Immunohistochemical analysis localized CSE to smooth muscle cells encircling arteries in stem villi. Immunoreactivity was reduced in placentas from pregnancies with severe early-onset growth-restriction and preeclampsia displaying abnormal umbilical artery Doppler waveforms compared with preeclamptic placentas with normal waveforms and controls. These findings were confirmed at the protein and mRNA levels. MicroRNA-21, which negatively regulates CSE expression, was increased in placentas with abnormal Doppler waveforms. Exposure of villus explants to hypoxia-reoxygenation significantly reduced CSE protein and mRNA and increased microRNA-21 expression. No changes were observed in cystathionine β-synthase expression, immunolocalized principally to the trophoblast, in pathologic placentas or in vitro. Finally, perfusion of normal placentas with an H(2)S donor, after preconstriction with a thromboxane mimetic, resulted in dose-dependent vasorelaxation. Glibenclamide and N(G)-nitro-l-arginine methyl ester partially blocked the effect, indicating that H(2)S acts through ATP-sensitive K(+) channels and nitric oxide synthesis. These results demonstrate that H(2)S is a powerful vasodilator of the placental vasculature and that expression of CSE is reduced in placentas associated with increased vascular resistance. American Society for Investigative Pathology 2013-04 /pmc/articles/PMC3608014/ /pubmed/23410520 http://dx.doi.org/10.1016/j.ajpath.2013.01.001 Text en © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator. |
spellingShingle | Regular Article Cindrova-Davies, Tereza Herrera, Emilio A. Niu, Youguo Kingdom, John Giussani, Dino A. Burton, Graham J. Reduced Cystathionine γ-Lyase and Increased miR-21 Expression Are Associated with Increased Vascular Resistance in Growth-Restricted Pregnancies: Hydrogen Sulfide as a Placental Vasodilator |
title | Reduced Cystathionine γ-Lyase and Increased miR-21 Expression Are Associated with Increased Vascular Resistance in Growth-Restricted Pregnancies: Hydrogen Sulfide as a Placental Vasodilator |
title_full | Reduced Cystathionine γ-Lyase and Increased miR-21 Expression Are Associated with Increased Vascular Resistance in Growth-Restricted Pregnancies: Hydrogen Sulfide as a Placental Vasodilator |
title_fullStr | Reduced Cystathionine γ-Lyase and Increased miR-21 Expression Are Associated with Increased Vascular Resistance in Growth-Restricted Pregnancies: Hydrogen Sulfide as a Placental Vasodilator |
title_full_unstemmed | Reduced Cystathionine γ-Lyase and Increased miR-21 Expression Are Associated with Increased Vascular Resistance in Growth-Restricted Pregnancies: Hydrogen Sulfide as a Placental Vasodilator |
title_short | Reduced Cystathionine γ-Lyase and Increased miR-21 Expression Are Associated with Increased Vascular Resistance in Growth-Restricted Pregnancies: Hydrogen Sulfide as a Placental Vasodilator |
title_sort | reduced cystathionine γ-lyase and increased mir-21 expression are associated with increased vascular resistance in growth-restricted pregnancies: hydrogen sulfide as a placental vasodilator |
topic | Regular Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3608014/ https://www.ncbi.nlm.nih.gov/pubmed/23410520 http://dx.doi.org/10.1016/j.ajpath.2013.01.001 |
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