TY - JOUR
T1 - Vascular endothelial mitochondrial oxidative stress in response to preeclampsia
T2 - a role for angiotension II type 1 autoantibodies
AU - Deer, Evangeline
AU - Vaka, V. Ramana
AU - McMaster, Kristen M.
AU - Wallace, Kedra
AU - Cornelius, Denise C.
AU - Amaral, Lorena M.
AU - Cunningham, Mark W.
AU - LaMarca, Babbette
N1 - Funding Information:
The authors report receiving financial support for the study material from the Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, Mississippi. E.D. reports receiving a T32 Trainee Grant from the American Heart Association (AHA) under grant number T32-HL105324. V.R.V. reports receiving a Predoctoral fellowship from the AHA under award number 17PRE33660592. D.C.C. reports receiving funding from the National Institutes of Health (NIH) under grant numbers R00HL130456 and P20GM104357. L.M.A. reports receiving financial support from the NIH under grant number P20GM121334 and an early career award from the AHA under award numer 19CDA34670055. M.W.C. reports receiving an early career award from the AHA under award number 18CDA34110264. B.L. reports receiving financial support from the NIH under grant numbers RO1HD067541-06 and P20GM121334.
Publisher Copyright:
© 2020 Elsevier Inc.
PY - 2021/1
Y1 - 2021/1
N2 - Background: Preeclampsia is characterized by a new onset of hypertension during pregnancy and is associated with autoantibodies against the angiotensin II type 1 receptor and oxidative stress. There is growing evidence for mitochondrial dysfunction in preeclampsia, however, the culprits for mitochondrial dysfunction are still being defined. We previously demonstrated that angiotensin II type 1 autoantibodies cause renal, placental, and endothelial mitochondrial dysfunction in pregnant rats. However, the role of the angiotensin II type 1 autoantibodies in endothelial mitochondrial function in response to sera from preeclamptics is unknown. Thus, we hypothesized that circulating factors, such as the angiotensin II type 1 autoantibodies, during preeclampsia would negatively impact the vascular endothelial mitochondrial function in human umbilical vein endothelial cells. Objective: The objective of the study was to determine a role for circulating angiotensin II type 1 autoantibodies to cause endothelial mitochondrial reactive oxygen species and dysfunction in preeclampsia compared to normal pregnant controls. Study Design: Immediately after delivery, sera was collected from preeclamptic patients and normal pregnant controls. The mitochondrial reactive oxygen species were determined from the cells treated overnight with 10% sera from either the control or preeclamptic patients with and without the antiotension II type 1 autoantibodies inhibitor peptide (‘n7AAc’). Results: Preeclampsia patients at <34 weeks’ gestation exhibited an elevated mean arterial blood pressure. Cells treated with serum from the preeclampsia patients at <34 weeks gestational age showed significantly (P<0.05) greater mitochondrial oxidative stress and reduced respiration than cells treated with the control sera, and these abnormalities were restored with ‘n7AAc’. Conclusion: This study demonstrates that endothelial mitochondrial dysfunction occurs in response to circulating factors, especially in response to serum from preterm preeclampsia patients, and can be restored by blocking circulating angiotensin II type 1 autoantibodies, thereby indicating a potential new therapeutic target for preeclampsia.
AB - Background: Preeclampsia is characterized by a new onset of hypertension during pregnancy and is associated with autoantibodies against the angiotensin II type 1 receptor and oxidative stress. There is growing evidence for mitochondrial dysfunction in preeclampsia, however, the culprits for mitochondrial dysfunction are still being defined. We previously demonstrated that angiotensin II type 1 autoantibodies cause renal, placental, and endothelial mitochondrial dysfunction in pregnant rats. However, the role of the angiotensin II type 1 autoantibodies in endothelial mitochondrial function in response to sera from preeclamptics is unknown. Thus, we hypothesized that circulating factors, such as the angiotensin II type 1 autoantibodies, during preeclampsia would negatively impact the vascular endothelial mitochondrial function in human umbilical vein endothelial cells. Objective: The objective of the study was to determine a role for circulating angiotensin II type 1 autoantibodies to cause endothelial mitochondrial reactive oxygen species and dysfunction in preeclampsia compared to normal pregnant controls. Study Design: Immediately after delivery, sera was collected from preeclamptic patients and normal pregnant controls. The mitochondrial reactive oxygen species were determined from the cells treated overnight with 10% sera from either the control or preeclamptic patients with and without the antiotension II type 1 autoantibodies inhibitor peptide (‘n7AAc’). Results: Preeclampsia patients at <34 weeks’ gestation exhibited an elevated mean arterial blood pressure. Cells treated with serum from the preeclampsia patients at <34 weeks gestational age showed significantly (P<0.05) greater mitochondrial oxidative stress and reduced respiration than cells treated with the control sera, and these abnormalities were restored with ‘n7AAc’. Conclusion: This study demonstrates that endothelial mitochondrial dysfunction occurs in response to circulating factors, especially in response to serum from preterm preeclampsia patients, and can be restored by blocking circulating angiotensin II type 1 autoantibodies, thereby indicating a potential new therapeutic target for preeclampsia.
KW - electron transport chain
KW - endothelial cells
KW - mitochondria
KW - oxidative stress
KW - placenta
KW - preeclampsia
KW - reactive oxygen species
UR - http://www.scopus.com/inward/record.url?scp=85100124932&partnerID=8YFLogxK
U2 - 10.1016/j.ajogmf.2020.100275
DO - 10.1016/j.ajogmf.2020.100275
M3 - Article
C2 - 33451592
AN - SCOPUS:85100124932
SN - 2589-9333
VL - 3
JO - American journal of obstetrics & gynecology MFM
JF - American journal of obstetrics & gynecology MFM
IS - 1
M1 - 100275
ER -