Vaka 2019 Am J Physiol Regul Integr Comp Physiol

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Vaka VR, Mcmasters KM, Cornelius DC, Ibrahim T, Jayaram A, Usry N, Cunningham MW Jr, Amaral LM, LaMarca BD (2019) Natural killer cells contribute to mitochondrial dysfunction in response to placental ischemia in Reduced Uterine Perfusion Pressure (RUPP) rats. Am J Physiol Regul Integr Comp Physiol [Epub ahead of print].

» PMID: 30811248

Vaka VR, Mcmasters KM, Cornelius DC, Ibrahim T, Jayaram A, Usry N, Cunningham MW Jr, Amaral LM, LaMarca BD (2019) Am J Physiol Regul Integr Comp Physiol

Abstract: Preeclampsia (PE) is characterized by new onset hypertension during pregnancy and is associated with immune activation and placental oxidative stress. Mitochondrial (mt) dysfunction is a major source of oxidative stress and may play a role in the pathology of PE. We have previously shown that placental ischemia is associated with mt 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 mt function associated with hypertension in the RUPP rat model of PE. Pregnant Sprague Dawley rats were divided into 3 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 (3.5µg/100µL, i.p) on Gday 15 and Gday 17. On GD19 blood pressure (MAP) was measured, placental mitochondria were isolated and used for mitochondrial assays. MAP was elevated in RUPP vs. 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. Endothelial cells (HUVEC) treated with RUPP+NKD serum restored respiration with reduced mtROS. The restored placental or endothelial mt function along with attenuated endothelial cell mtROS with NK cell depletion indicate an important role of NK cells in mediating mt oxidative stress in the pathology of PE.

Keywords: Natural Killer cells, Placental ischemia, Mitochondria, Oxidative stress Bioblast editor: Plangger M


Labels: MiParea: Respiration 

Stress:Ischemia-reperfusion, Oxidative stress;RONS  Organism: Human, Rat  Tissue;cell: Endothelial;epithelial;mesothelial cell, Genital  Preparation: Intact cells, Isolated mitochondria  Enzyme: Complex I, Complex IV;cytochrome c oxidase 

Coupling state: LEAK, OXPHOS, ET  Pathway: N, CIV, ROX  HRR: Oxygraph-2k 

Labels, 2019-03