Characterization of mitochondrial bioenergetics in preeclampsia

Ramana Vaka, Evangeline Deer, Mark Cunningham, Kristen M. McMaster, Kedra Wallace, Denise C. Cornelius, Lorena M. Amaral, Babbette Lamarca

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

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 patientʹs 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.

Original languageEnglish
Article number5063
JournalJournal of Clinical Medicine
Volume10
Issue number21
DOIs
StatePublished - 1 Nov 2021

Keywords

  • Electron transport chain
  • Mitochondria
  • Oxidative stress
  • Placenta
  • Preeclampsia
  • Reactive oxygen species

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