Therapeutically targeting mitochondrial redox signalling alleviates endothelial dysfunction in preeclampsia
| dc.contributor.author | McCarthy, Cathal M. | |
| dc.contributor.author | Kenny, Louise C. | |
| dc.contributor.funder | Science Foundation Ireland | en |
| dc.date.accessioned | 2016-10-17T11:37:35Z | |
| dc.date.available | 2016-10-17T11:37:35Z | |
| dc.date.issued | 2016-09-08 | |
| dc.date.updated | 2016-10-17T11:29:30Z | |
| 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.description.status | Peer reviewed | en |
| dc.description.version | Published Version | en |
| dc.format.mimetype | application/pdf | en |
| dc.identifier.articleid | 32683 | |
| 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.doi | 10.1038/srep32683 | |
| dc.identifier.endpage | 32694 | en |
| dc.identifier.issn | 2045-2322 | |
| dc.identifier.issued | 6 | en |
| dc.identifier.journaltitle | Scientific Reports | en |
| dc.identifier.startpage | 32683 | en |
| dc.identifier.uri | https://hdl.handle.net/10468/3185 | |
| dc.identifier.volume | 8 | 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 |
