Department of Biophysics and Pharmacology, Institute of Biosciences of Botucatu (IBB), São Paulo State University (UNESP), Botucatu 18618-689, SP, Brazil.
Biotechnology Institute (IBTEC), São Paulo State University (UNESP), Botucatu 18618-687, SP, Brazil.
Int J Mol Sci. 2024 Aug 10;25(16):8738. doi: 10.3390/ijms25168738.
Preeclampsia (PE) is a hypertensive pregnancy syndrome associated with target organ damage and increased cardiovascular risks, necessitating antihypertensive therapy. However, approximately 40% of patients are nonresponsive to treatment, which results in worse clinical outcomes. This study aimed to compare circulating proteomic profiles and identify differentially expressed proteins among 10 responsive (R-PE), 10 nonresponsive (NR-PE) patients, and 10 healthy pregnant controls (HP). We also explored correlations between these proteins and clinical data. Plasma protein relative quantification was performed using mass spectrometry, followed by bioinformatics analyses with the UniProt database, PatternLab for Proteomics 4.0, and MetaboAnalyst software (version 6.0). Considering a fold change of 1.5, four proteins were differentially expressed between NR-PE and R-PE: one upregulated (fibronectin) and three downregulated (pregnancy-specific beta-1-glycoprotein 1, complement C4B, and complement C4A). Between NR-PE and HP, six proteins were differentially expressed: two upregulated (clusterin and plasmin heavy chain A) and four downregulated (apolipoprotein L1, heparin cofactor II, complement C4B, and haptoglobin-related protein). Three proteins were differentially expressed between R-PE and HP: one downregulated (transthyretin) and two upregulated (apolipoprotein C1 and hemoglobin subunit beta). These findings suggest a complex interplay of these proteins involved in inflammatory, immune, and metabolic processes with antihypertensive therapy responsiveness and PE pathophysiology.
子痫前期（PE）是一种与靶器官损伤和心血管风险增加相关的妊娠高血压综合征，需要进行降压治疗。然而，约 40%的患者对治疗无反应，导致临床结局更差。本研究旨在比较循环蛋白质组谱，并在 10 例反应性（R-PE）、10 例无反应性（NR-PE）患者和 10 例健康妊娠对照（HP）中识别差异表达的蛋白质。我们还探讨了这些蛋白质与临床数据之间的相关性。使用质谱法进行血浆蛋白质相对定量，然后使用 UniProt 数据库、PatternLab for Proteomics 4.0 和 MetaboAnalyst 软件（版本 6.0）进行生物信息学分析。考虑到 1.5 倍的变化倍数，NR-PE 和 R-PE 之间有 4 种蛋白质表达差异：一种上调（纤连蛋白）和三种下调（妊娠特异性β-1-糖蛋白 1、补体 C4B 和补体 C4A）。NR-PE 和 HP 之间有 6 种蛋白质表达差异：两种上调（载脂蛋白 L1、肝素辅因子 II、补体 C4B 和触珠蛋白相关蛋白）和四种下调（簇蛋白和纤溶酶原重链 A）。R-PE 和 HP 之间有 3 种蛋白质表达差异：一种下调（转甲状腺素蛋白）和两种上调（载脂蛋白 C1 和血红蛋白亚基β）。这些发现表明，这些参与炎症、免疫和代谢过程的蛋白质与降压治疗反应性和 PE 病理生理学之间存在复杂的相互作用。
