1 Molecular Medicine Laboratory, Unidad Académica de Medicina Humana y Ciencias de la Salud, Universidad Autónoma de Zacatecas, 98160 Zacatecas, México.
2 Posgrado en Ingeniería y Tecnología Aplicada, Unidad Académica de Ingeniería Eléctrica, Universidad Autónoma de Zacatecas, 98000 Zacatecas, México.
Exp Biol Med (Maywood). 2018 Mar;243(6):576-585. doi: 10.1177/1535370218755690. Epub 2018 Feb 7.
Preeclampsia (PE) is a pregnancy complex disease, distinguished by high blood pressure and proteinuria, diagnosed after the 20th gestation week. Depending on the values of blood pressure, urine protein concentrations, symptomatology, and onset of disease there is a wide range of phenotypes, from mild forms developing predominantly at the end of pregnancy to severe forms developing in the early stage of pregnancy. In the worst cases severe forms of PE could lead to systemic endothelial dysfunction, eclampsia, and maternal and/or fetal death. Worldwide the fetal morbidity and mortality related to PE is calculated to be around 8% of the total pregnancies. PE still being an enigma regarding its etiology and pathophysiology, in general a deficient trophoblast invasion during placentation at first stage of pregnancy, in combination with maternal conditions are accepted as a cause of endothelial dysfunction, inflammatory alterations and appearance of symptoms. Depending on the PE multifactorial origin, several in vitro, in vivo, and in silico models have been used to evaluate the PE pathophysiology as well as to identify or test biomarkers predicting, diagnosing or prognosing the syndrome. This review focuses on the most common models used for the study of PE, including those related to placental development, abnormal trophoblast invasion, uteroplacental ischemia, angiogenesis, oxygen deregulation, and immune response to maternal-fetal interactions. The advances in mathematical and computational modeling of metabolic network behavior, gene prioritization, the protein-protein interaction network, the genetics of PE, and the PE prediction/classification are discussed. Finally, the potential of these models to enable understanding of PE pathogenesis and to evaluate new preventative and therapeutic approaches in the management of PE are also highlighted. Impact statement This review is important to the field of preeclampsia (PE), because it provides a description of the principal in vitro, in vivo, and in silico models developed for the study of its principal aspects, and to test emerging therapies or biomarkers predicting the syndrome before their evaluation in clinical trials. Despite the current advance, the field still lacking of new methods and original modeling approaches that leads to new knowledge about pathophysiology. The part of in silico models described in this review has not been considered in the previous reports.
子痫前期（PE）是一种妊娠复杂疾病，以高血压和蛋白尿为特征，在妊娠 20 周后诊断。根据血压值、尿蛋白浓度、症状和疾病发作，存在广泛的表型，从轻度形式主要在妊娠晚期发展到重度形式在妊娠早期发展。在最坏的情况下，严重的子痫前期形式可能导致全身内皮功能障碍、子痫和母亲和/或胎儿死亡。全世界与子痫前期相关的胎儿发病率和死亡率估计约为总妊娠的 8%。PE 的病因和病理生理学仍然是一个谜，一般认为是妊娠早期胎盘形成时滋养细胞侵袭不足，加上母体状况，导致内皮功能障碍、炎症改变和症状出现。根据 PE 的多因素起源，已经使用了几种体外、体内和计算模型来评估 PE 的病理生理学，以及识别或测试预测、诊断或预测该综合征的生物标志物。本综述重点介绍了用于研究 PE 的最常见模型，包括与胎盘发育、异常滋养细胞侵袭、子宫胎盘缺血、血管生成、氧调节以及对母体-胎儿相互作用的免疫反应相关的模型。讨论了代谢网络行为、基因优先级、蛋白质-蛋白质相互作用网络、PE 遗传学和 PE 预测/分类的数学和计算建模方面的进展。最后，还强调了这些模型在理解 PE 发病机制以及评估预防和治疗新方法在 PE 管理中的潜力。
声明 本文对子痫前期（PE）领域很重要，因为它描述了为研究其主要方面而开发的主要体外、体内和计算模型，并测试了新的治疗方法或预测该综合征的生物标志物，然后再在临床试验中进行评估。尽管目前有所进展，但该领域仍缺乏新的方法和原始建模方法，无法获得关于病理生理学的新知识。本文中描述的计算模型部分在以前的报告中没有被考虑。
