PMID- 30811248
OWN - NLM
STAT- MEDLINE
DCOM- 20200219
LR  - 20200930
IS  - 1522-1490 (Electronic)
IS  - 0363-6119 (Print)
IS  - 0363-6119 (Linking)
VI  - 316
IP  - 5
DP  - 2019 May 1
TI  - Natural killer cells contribute to mitochondrial dysfunction in response to 
      placental ischemia in reduced uterine perfusion pressure rats.
PG  - R441-R447
LID - 10.1152/ajpregu.00279.2018 [doi]
AB  - Preeclampsia (PE) is characterized by new-onset hypertension during pregnancy and 
      is associated with immune activation and placental oxidative stress. 
      Mitochondrial dysfunction is a major source of oxidative stress and may play a 
      role in the pathology of PE. We (Vaka VR, et al. Hypertension 72: 703-711, 2018. 
      doi: 10.1161/HYPERTENSIONAHA.118.11290 .) have previously shown that placental 
      ischemia is associated with mitochondrial oxidative stress in the reduced uterine 
      perfusion pressure (RUPP) model of PE. Furthermore, we have also shown that 
      placental ischemia induces natural killer (NK) cell activation in RUPP. Thus, we 
      hypothesize that NK cell depletion could improve mitochondrial function 
      associated with hypertension in the RUPP rat model of PE. Pregnant Sprague-Dawley 
      rats were divided into three groups: normal pregnant (NP), RUPP, and RUPP+NK cell 
      depletion rats (RUPP+NKD). On gestational day (GD)14, RUPP surgery was performed, 
      and NK cells were depleted by administering anti-asialo GM1 antibodies (3.5 
      microg/100 microl ip) on GD15 and GD17. On GD19, mean arterial pressure (MAP) was 
      measured, and placental mitochondria were isolated and used for mitochondrial 
      assays. MAP was elevated in RUPP versus NP rats (119 +/- 1 vs.104 +/- 2 mmHg, P = 
      0.0004) and was normalized in RUPP+NKD rats (107 +/- 2 mmHg, P = 0.002). Reduced 
      complex IV activity and state 3 respiration rate were improved in RUPP+NKD rats. 
      Human umbilical vein endothelial cells treated with RUPP+NKD serum restored 
      respiration with reduced mitochondrial reactive oxygen species (ROS). The 
      restored placental or endothelial mitochondrial function along with attenuated 
      endothelial cell mitochondrial ROS with NK cell depletion indicate an important 
      role of NK cells in mediating mitochondrial oxidative stress in the pathology of 
      PE.
FAU - Vaka, Venkata Ramana
AU  - Vaka VR
AD  - Department of Pharmacology and Toxicology, University of Mississippi Medical 
      Center , Jackson, Mississippi.
FAU - McMaster, Kristen M
AU  - McMaster KM
AD  - Department of Obstetrics and Gynecology, University of Mississippi Medical Center 
      , Jackson, Mississippi.
FAU - Cornelius, Denise C
AU  - Cornelius DC
AD  - Department of Emergency Medicine, University of Mississippi Medical Center , 
      Jackson, Mississippi.
FAU - Ibrahim, Tarek
AU  - Ibrahim T
AD  - Department of Pharmacology and Toxicology, University of Mississippi Medical 
      Center , Jackson, Mississippi.
FAU - Jayaram, Aswathi
AU  - Jayaram A
AD  - Department of Obstetrics and Gynecology, University of Mississippi Medical Center 
      , Jackson, Mississippi.
FAU - Usry, Nathan
AU  - Usry N
AD  - Department of Pharmacology and Toxicology, University of Mississippi Medical 
      Center , Jackson, Mississippi.
FAU - Cunningham, Mark W Jr
AU  - Cunningham MW Jr
AD  - Department of Pharmacology and Toxicology, University of Mississippi Medical 
      Center , Jackson, Mississippi.
FAU - Amaral, Lorena M
AU  - Amaral LM
AD  - Department of Pharmacology and Toxicology, University of Mississippi Medical 
      Center , Jackson, Mississippi.
FAU - LaMarca, Babbette
AU  - LaMarca B
AD  - Department of Pharmacology and Toxicology, University of Mississippi Medical 
      Center , Jackson, Mississippi.
AD  - Department of Obstetrics and Gynecology, University of Mississippi Medical Center 
      , Jackson, Mississippi.
LA  - eng
GR  - P20 GM121334/GM/NIGMS NIH HHS/United States
GR  - R01 HD067541/HD/NICHD NIH HHS/United States
GR  - T32 HL105324/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20190227
PL  - United States
TA  - Am J Physiol Regul Integr Comp Physiol
JT  - American journal of physiology. Regulatory, integrative and comparative 
      physiology
JID - 100901230
RN  - 0 (Reactive Oxygen Species)
SB  - IM
MH  - Animals
MH  - Arterial Pressure
MH  - Cell Respiration
MH  - Cells, Cultured
MH  - Disease Models, Animal
MH  - *Energy Metabolism
MH  - Female
MH  - Gestational Age
MH  - Human Umbilical Vein Endothelial Cells/immunology/metabolism
MH  - Humans
MH  - Ischemia/immunology/*metabolism/physiopathology
MH  - Killer Cells, Natural/immunology/*metabolism
MH  - Mitochondria/*metabolism
MH  - *Oxidative Stress
MH  - Placenta/*blood supply
MH  - Pre-Eclampsia/immunology/*metabolism/physiopathology
MH  - Pregnancy
MH  - Rats, Sprague-Dawley
MH  - Reactive Oxygen Species/metabolism
MH  - Regional Blood Flow
MH  - Uterus/*blood supply
PMC - PMC6589603
OTO - NOTNLM
OT  - mitochondria
OT  - natural killer cells
OT  - placental ischemia
OT  - reactive oxygen species
COIS- No conflicts of interest, financial or otherwise, are declared by the authors.
EDAT- 2019/02/28 06:00
MHDA- 2020/02/20 06:00
PMCR- 2020/05/01
CRDT- 2019/02/28 06:00
PHST- 2019/02/28 06:00 [pubmed]
PHST- 2020/02/20 06:00 [medline]
PHST- 2019/02/28 06:00 [entrez]
PHST- 2020/05/01 00:00 [pmc-release]
AID - R-00279-2018 [pii]
AID - 10.1152/ajpregu.00279.2018 [doi]
PST - ppublish
SO  - Am J Physiol Regul Integr Comp Physiol. 2019 May 1;316(5):R441-R447. doi: 
      10.1152/ajpregu.00279.2018. Epub 2019 Feb 27.