Characterization of Mitochondrial Bioenergetics in Preeclampsia

Preeclampsia (PE) is characterized by new onset hypertension during pregnancy and is associated with oxidative stress, placental ischemia, and autoantibodies to the angiotensin II type I receptor (AT1-AA). Mitochondrial (mt) dysfunction in PE and various sources of oxidative stress, such as monocyte...

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Autores principales:	Ramana Vaka, Evangeline Deer, Mark Cunningham, Kristen M. McMaster, Kedra Wallace, Denise C. Cornelius, Lorena M. Amaral, Babbette LaMarca
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	mitochondria electron transport chain oxidative stress preeclampsia placenta reactive oxygen species Medicine R
Acceso en línea:	https://doaj.org/article/6e6230f1b5084f079d7ceaa5c0a56261
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spelling	oai:doaj.org-article:6e6230f1b5084f079d7ceaa5c0a562612021-11-11T17:41:15ZCharacterization of Mitochondrial Bioenergetics in Preeclampsia10.3390/jcm102150632077-0383https://doaj.org/article/6e6230f1b5084f079d7ceaa5c0a562612021-10-01T00:00:00Zhttps://www.mdpi.com/2077-0383/10/21/5063https://doaj.org/toc/2077-0383Preeclampsia (PE) is characterized by new onset hypertension during pregnancy and is associated with oxidative stress, placental ischemia, and autoantibodies to the angiotensin II type I receptor (AT1-AA). Mitochondrial (mt) dysfunction in PE and various sources of oxidative stress, such as monocytes, neutrophils, and CD4 + T cells, have been identified as important players in the pathophysiology of PE. We have established the significance of AT1-AA, TNF-α, and CD4 + T cells in causing mitochondrial (mt) dysfunction in renal and placental tissues in pregnant rats. Although the role of mt dysfunction from freshly isolated intact placental mitochondria has been compared in human PE and normally pregnant (NP) controls, variations among preterm PE or term PE have not been compared and mechanisms contributing to mt ROS during PE are unclear. Therefore, we hypothesized PE placentas would exhibit impaired placental mt function, which would be worse in preterm PE patients than in those of later gestational ages. Immediately after delivery, PE and NP patient’s placentas were collected, mt were isolated and mt respiration and ROS were measured. PE patients at either < or >34 weeks gestational age (GA) exhibited elevated blood pressure and decreased placental mt respiration rates (state 3 and maximal). Patients delivering at >34 weeks exhibited decreased Complex IV activity and expression. Placental mtROS was significantly reduced in both PE groups, compared to NP placental mitochondria. Collectively, the study demonstrates that PE mt dysfunction occurs in the placenta, with mtROS being lower than that seen in NP controls. These data indicate why antioxidants, as a potential target or new therapeutic agent, may not be ideal in treating the oxidative stress associated with PE.Ramana VakaEvangeline DeerMark CunninghamKristen M. McMasterKedra WallaceDenise C. CorneliusLorena M. AmaralBabbette LaMarcaMDPI AGarticlemitochondriaelectron transport chainoxidative stresspreeclampsiaplacentareactive oxygen speciesMedicineRENJournal of Clinical Medicine, Vol 10, Iss 5063, p 5063 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	mitochondria electron transport chain oxidative stress preeclampsia placenta reactive oxygen species Medicine R
spellingShingle	mitochondria electron transport chain oxidative stress preeclampsia placenta reactive oxygen species Medicine R Ramana Vaka Evangeline Deer Mark Cunningham Kristen M. McMaster Kedra Wallace Denise C. Cornelius Lorena M. Amaral Babbette LaMarca Characterization of Mitochondrial Bioenergetics in Preeclampsia
description	Preeclampsia (PE) is characterized by new onset hypertension during pregnancy and is associated with oxidative stress, placental ischemia, and autoantibodies to the angiotensin II type I receptor (AT1-AA). Mitochondrial (mt) dysfunction in PE and various sources of oxidative stress, such as monocytes, neutrophils, and CD4 + T cells, have been identified as important players in the pathophysiology of PE. We have established the significance of AT1-AA, TNF-α, and CD4 + T cells in causing mitochondrial (mt) dysfunction in renal and placental tissues in pregnant rats. Although the role of mt dysfunction from freshly isolated intact placental mitochondria has been compared in human PE and normally pregnant (NP) controls, variations among preterm PE or term PE have not been compared and mechanisms contributing to mt ROS during PE are unclear. Therefore, we hypothesized PE placentas would exhibit impaired placental mt function, which would be worse in preterm PE patients than in those of later gestational ages. Immediately after delivery, PE and NP patient’s placentas were collected, mt were isolated and mt respiration and ROS were measured. PE patients at either < or >34 weeks gestational age (GA) exhibited elevated blood pressure and decreased placental mt respiration rates (state 3 and maximal). Patients delivering at >34 weeks exhibited decreased Complex IV activity and expression. Placental mtROS was significantly reduced in both PE groups, compared to NP placental mitochondria. Collectively, the study demonstrates that PE mt dysfunction occurs in the placenta, with mtROS being lower than that seen in NP controls. These data indicate why antioxidants, as a potential target or new therapeutic agent, may not be ideal in treating the oxidative stress associated with PE.
format	article
author	Ramana Vaka Evangeline Deer Mark Cunningham Kristen M. McMaster Kedra Wallace Denise C. Cornelius Lorena M. Amaral Babbette LaMarca
author_facet	Ramana Vaka Evangeline Deer Mark Cunningham Kristen M. McMaster Kedra Wallace Denise C. Cornelius Lorena M. Amaral Babbette LaMarca
author_sort	Ramana Vaka
title	Characterization of Mitochondrial Bioenergetics in Preeclampsia
title_short	Characterization of Mitochondrial Bioenergetics in Preeclampsia
title_full	Characterization of Mitochondrial Bioenergetics in Preeclampsia
title_fullStr	Characterization of Mitochondrial Bioenergetics in Preeclampsia
title_full_unstemmed	Characterization of Mitochondrial Bioenergetics in Preeclampsia
title_sort	characterization of mitochondrial bioenergetics in preeclampsia
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/6e6230f1b5084f079d7ceaa5c0a56261
work_keys_str_mv	AT ramanavaka characterizationofmitochondrialbioenergeticsinpreeclampsia AT evangelinedeer characterizationofmitochondrialbioenergeticsinpreeclampsia AT markcunningham characterizationofmitochondrialbioenergeticsinpreeclampsia AT kristenmmcmaster characterizationofmitochondrialbioenergeticsinpreeclampsia AT kedrawallace characterizationofmitochondrialbioenergeticsinpreeclampsia AT deniseccornelius characterizationofmitochondrialbioenergeticsinpreeclampsia AT lorenamamaral characterizationofmitochondrialbioenergeticsinpreeclampsia AT babbettelamarca characterizationofmitochondrialbioenergeticsinpreeclampsia
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Characterization of Mitochondrial Bioenergetics in Preeclampsia

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