TY - JOUR
T1 - Characterization of mitochondrial bioenergetics in preeclampsia
AU - Vaka, Ramana
AU - Deer, Evangeline
AU - Cunningham, Mark
AU - McMaster, Kristen M.
AU - Wallace, Kedra
AU - Cornelius, Denise C.
AU - Amaral, Lorena M.
AU - Lamarca, Babbette
N1 - Funding Information:
Funding: This study was supported by NIH R01HD067541 and P20GM121334 grants to B. LaMarca, R00HL130456 and P20GM104357 grants to D.C. Cornelius, 17PRE33660592/AHA predoctoral fellowship to V.R. Vaka, T32 Trainee Grant T32‐HL105324 to E. Deer, American heart association (AHA) early career award 19CDA34670055 to L.M. Amaral.
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/11/1
Y1 - 2021/11/1
N2 - 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.
AB - 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.
KW - Electron transport chain
KW - Mitochondria
KW - Oxidative stress
KW - Placenta
KW - Preeclampsia
KW - Reactive oxygen species
UR - http://www.scopus.com/inward/record.url?scp=85118113369&partnerID=8YFLogxK
U2 - 10.3390/jcm10215063
DO - 10.3390/jcm10215063
M3 - Article
AN - SCOPUS:85118113369
SN - 2077-0383
VL - 10
JO - Journal of Clinical Medicine
JF - Journal of Clinical Medicine
IS - 21
M1 - 5063
ER -