Vaka Ramana, Deer Evangeline, Cunningham Mark, McMaster Kristen M, Wallace Kedra, Cornelius Denise C, Amaral Lorena M, LaMarca Babbette
Department of Pharmacology, Physiology & Toxicology, Center for Excellence in Cardiovascular and Renal Research, University of Mississippi Medical Center, Jackson, MS 39216, USA.
Department of Obstetrics and Gynecology, Center for Excellence in Cardiovascular and Renal Research, University of Mississippi Medical Center, Jackson, MS 39216, USA.
J Clin Med. 2021 Oct 29;10(21):5063. doi: 10.3390/jcm10215063.
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 patient's 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.
子痫前期（PE）的特征是孕期新发高血压，与氧化应激、胎盘缺血以及血管紧张素II 1型受体自身抗体（AT1-AA）有关。已确定PE中的线粒体（mt）功能障碍以及各种氧化应激源，如单核细胞、中性粒细胞和CD4 + T细胞，是PE病理生理学中的重要因素。我们已经确定了AT1-AA、TNF-α和CD4 + T细胞在导致孕鼠肾脏和胎盘组织线粒体（mt）功能障碍中的作用。虽然已比较了新鲜分离的完整胎盘线粒体中mt功能障碍在人类PE和正常妊娠（NP）对照中的作用，但未比较早产PE或足月PE之间的差异，且PE期间导致mt活性氧（mtROS）的机制尚不清楚。因此，我们假设PE胎盘会表现出胎盘mt功能受损，早产PE患者的受损情况会比孕周较大者更严重。分娩后立即收集PE和NP患者的胎盘，分离mt并测量mt呼吸和ROS。孕周<或>34周（GA）的PE患者血压升高，胎盘mt呼吸率（状态3和最大值）降低。孕周>34周分娩的患者复合物IV活性和表达降低。与NP胎盘线粒体相比，两个PE组的胎盘mtROS均显著降低。总体而言，该研究表明PE的mt功能障碍发生在胎盘中，mtROS低于NP对照。这些数据表明了为什么抗氧化剂作为一种潜在靶点或新型治疗药物，在治疗与PE相关的氧化应激方面可能并不理想。
