Institute of Cardiovascular and Medical Sciences, University of Glasgow, Scotland, United Kingdom.
Experimental and Clinical Research Center, a joint cooperation between Max-Delbrück-Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, Berlin, Germany.
Physiol Genomics. 2021 Jun 1;53(6):259-268. doi: 10.1152/physiolgenomics.00160.2020. Epub 2021 May 10.
Preexisting or new onset of hypertension affects pregnancy and is one of the leading causes of maternal and fetal morbidity and mortality. In certain cases, it also leads to long-term maternal cardiovascular complications. The placenta is a key player in the pathogenesis of complicated hypertensive pregnancies, however the pathomechanisms leading to an abnormal placenta are poorly understood. In this study, we compared the placental proteome of two pregnant hypertensive models with their corresponding normotensive controls: a preexisting hypertension pregnancy model (stroke-prone spontaneously hypertensive rats; SHRSP) versus Wistar-Kyoto and the transgenic RAS activated gestational hypertension model (transgenic for human angiotensinogen Sprague-Dawley rats; SD-PE) versus Sprague-Dawley rats, respectively. Label-free proteomics using nano LC-MS/MS was performed for identification and quantification of proteins. Between the two models, we found widespread differences in the expression of placental proteins including those related to hypertension, inflammation, and trophoblast invasion, whereas pathways such as regulation of serine endopeptidase activity, tissue injury response, coagulation, and complement activation were enriched in both models. We present for the first time the placental proteome of SHRSP and SD-PE and provide insight into the molecular make-up of models of hypertensive pregnancy. Our study informs future research into specific preeclampsia and chronic hypertension pregnancy mechanisms and translation of rodent data to the clinic.
先前存在或新发生的高血压会影响妊娠，是孕产妇和胎儿发病率和死亡率的主要原因之一。在某些情况下，它还会导致长期的母体心血管并发症。胎盘是复杂妊娠高血压发病机制的关键因素，然而导致胎盘异常的病理机制还知之甚少。在这项研究中，我们比较了两种妊娠高血压模型（自发性高血压脑卒中倾向大鼠（SHRSP）与 Wistar-Kyoto 大鼠的预先存在的高血压妊娠模型和转人类血管紧张素原的 Sprague-Dawley 大鼠（SD-PE）与 Sprague-Dawley 大鼠的转基因 RAS 激活的妊娠高血压模型）与其相应的正常血压对照组的胎盘蛋白质组。使用纳升 LC-MS/MS 进行无标记蛋白质组学分析，以鉴定和定量蛋白质。在这两种模型之间，我们发现胎盘蛋白的表达存在广泛差异，包括与高血压、炎症和滋养细胞浸润相关的蛋白，而调节丝氨酸内肽酶活性、组织损伤反应、凝血和补体激活等途径在两种模型中均有富集。我们首次提供了 SHRSP 和 SD-PE 的胎盘蛋白质组图谱，并深入了解了妊娠高血压模型的分子构成。我们的研究为特定的子痫前期和慢性高血压妊娠机制的未来研究以及将啮齿动物数据转化为临床提供了信息。
