Murthi Padma, Pinar Anita A, Dimitriadis Evdokia, Samuel Chrishan S
Cardiovascular Disease Program, Monash Biomedicine Discovery Institute and Department of Pharmacology, Monash University, Victoria 3168, Australia.
Hudson Institute of Medical Research, Clayton, Victoria 3168, Australia.
Int J Mol Sci. 2020 Feb 19;21(4):1406. doi: 10.3390/ijms21041406.
Preeclampsia (PE) is a pregnancy-specific multisystem disorder and is associated with maladaptation of the maternal cardiovascular system and abnormal placentation. One of the important characteristics in the pathophysiology of PE is a dysfunction of the placenta. Placental insufficiency is associated with poor trophoblast uterine invasion and impaired transformation of the uterine spiral arterioles to high capacity and low impedance vessels and/or abnormalities in the development of chorionic villi. Significant progress in identifying potential molecular targets in the pathophysiology of PE is underway. The human placenta is immunologically functional with the trophoblast able to generate specific and diverse innate immune-like responses through their expression of multimeric self-assembling protein complexes, termed inflammasomes. However, the type of response is highly dependent upon the stimuli, the receptor(s) expressed and activated, the downstream signaling pathways involved, and the timing of gestation. Recent findings highlight that inflammasomes can act as a molecular link for several components at the syncytiotrophoblast surface and also in maternal blood thereby directly influencing each other. Thus, the inflammasome molecular platform can promote adverse inflammatory effects when chronically activated. This review highlights current knowledge in placental inflammasome expression and activity in PE-affected pregnancies, and consequently, vascular dysfunction in PE that must be addressed as an interdependent interactive process.
子痫前期(PE)是一种妊娠特有的多系统疾病,与母体心血管系统适应不良和胎盘形成异常有关。PE病理生理学的一个重要特征是胎盘功能障碍。胎盘功能不全与滋养细胞子宫侵袭不良、子宫螺旋小动脉向高容量和低阻抗血管转化受损和/或绒毛膜绒毛发育异常有关。在确定PE病理生理学中潜在分子靶点方面正在取得重大进展。人类胎盘具有免疫功能,滋养细胞能够通过表达称为炎性小体的多聚体自组装蛋白复合物产生特异性和多样化的固有免疫样反应。然而,反应类型高度依赖于刺激、表达和激活的受体、涉及的下游信号通路以及妊娠时间。最近的研究结果强调,炎性小体可以作为合体滋养层表面以及母体血液中几种成分的分子联系,从而直接相互影响。因此,炎性小体分子平台在长期激活时可促进不良炎症效应。本综述强调了目前关于PE影响的妊娠中胎盘炎性小体表达和活性的知识,以及因此PE中的血管功能障碍,这必须作为一个相互依存的交互过程来解决。