Therapeutically targeting mitochondrial redox signalling alleviates endothelial dysfunction in preeclampsia

Show simple item record

dc.contributor.author McCarthy, Cathal M.
dc.contributor.author Kenny, Louise C.
dc.date.accessioned 2016-10-17T11:37:35Z
dc.date.available 2016-10-17T11:37:35Z
dc.date.issued 2016-09-08
dc.identifier.citation McCarthy CM, Kenny LC (2016) 'Therapeutically targeting mitochondrial redox signalling alleviates endothelial dysfunction in preeclampsia'. Scientific Reports, 8 (6):32683-32694. doi: 10.1038/srep32683 en
dc.identifier.volume 8 en
dc.identifier.issued 6 en
dc.identifier.startpage 32683 en
dc.identifier.endpage 32694 en
dc.identifier.issn 2045-2322
dc.identifier.uri http://hdl.handle.net/10468/3185
dc.identifier.doi 10.1038/srep32683
dc.description.abstract Aberrant placentation generating placental oxidative stress is proposed to play a critical role in the pathophysiology of preeclampsia. Unfortunately, therapeutic trials of antioxidants have been uniformly disappointing. There is provisional evidence implicating mitochondrial dysfunction as a source of oxidative stress in preeclampsia. Here we provide evidence that mitochondrial reactive oxygen species mediates endothelial dysfunction and establish that directly targeting mitochondrial scavenging may provide a protective role. Human umbilical vein endothelial cells exposed to 3% plasma from women with pregnancies complicated by preeclampsia resulted in a significant decrease in mitochondrial function with a subsequent significant increase in mitochondrial superoxide generation compared to cells exposed to plasma from women with uncomplicated pregnancies. Real-time PCR analysis showed increased expression of inflammatory markers TNF-α, TLR-9 and ICAM-1 respectively in endothelial cells treated with preeclampsia plasma. MitoTempo is a mitochondrial-targeted antioxidant, pre-treatment of cells with MitoTempo protected against hydrogen peroxide-induced cell death. Furthermore MitoTempo significantly reduced mitochondrial superoxide production in cells exposed to preeclampsia plasma by normalising mitochondrial metabolism. MitoTempo significantly altered the inflammatory profile of plasma treated cells. These novel data support a functional role for mitochondrial redox signaling in modulating the pathogenesis of preeclampsia and identifies mitochondrial-targeted antioxidants as potential therapeutic candidates. en
dc.description.sponsorship Science Foundation Ireland (Program Grant for INFANT 12/RC/2272) en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher Nature Publishing Group en
dc.relation.uri http://www.ncbi.nlm.nih.gov/pubmed/27604418
dc.rights Copyright © 2016, The Author(s) This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ en
dc.rights.uri http://creativecommons.org/licenses/by/4.0/ en
dc.subject Mechanisms of disease en
dc.subject Molecular medicine en
dc.title Therapeutically targeting mitochondrial redox signalling alleviates endothelial dysfunction in preeclampsia en
dc.type Article (peer-reviewed) en
dc.internal.authorcontactother Cathal Mccarthy, Obstetrics & Gynaecology, University College Cork, Cork, Ireland. +353-21-490-3000 Email: cmccarthy@ucc.ie en
dc.internal.availability Full text available en
dc.date.updated 2016-10-17T11:29:30Z
dc.description.version Published Version en
dc.internal.rssid 363808856
dc.contributor.funder Science Foundation Ireland en
dc.description.status Peer reviewed en
dc.identifier.journaltitle Scientific Reports en
dc.internal.copyrightchecked Yes en
dc.internal.licenseacceptance Yes en
dc.internal.IRISemailaddress cmccarthy@ucc.ie en
dc.identifier.articleid 32683


Files in this item

This item appears in the following Collection(s)

Show simple item record

Copyright © 2016, The Author(s) This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ Except where otherwise noted, this item's license is described as Copyright © 2016, The Author(s) This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
This website uses cookies. By using this website, you consent to the use of cookies in accordance with the UCC Privacy and Cookies Statement. For more information about cookies and how you can disable them, visit our Privacy and Cookies statement