期刊
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY
卷 316, 期 5, 页码 R441-R447出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpregu.00279.2018
关键词
mitochondria; natural killer cells; placental ischemia; reactive oxygen species
类别
资金
- National Institutes of Health/Office of Research, UMMC [RO1 HD-067541, P20 GM-121334]
- [R00 HL-130456]
- [17PRE33660592/AHA]
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 mu g/100 mu l 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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据