Yin Aiqi, Guan Xiaonian, Zhang Jian V, Niu Jianmin
Department of Obstetrics, Shenzhen Maternity and Child Healthcare Hospital, The First School of Clinical Medicine, Southern Medical University, Shenzhen, China.
Center for Energy Metabolism and Reproduction, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
Front Cell Dev Biol. 2022 Sep 14;10:959239. doi: 10.3389/fcell.2022.959239. eCollection 2022.
Preeclampsia, a clinical syndrome mainly characterized by hypertension and proteinuria, with a worldwide incidence of 3-8% and high maternal mortality, is a risk factor highly associated with maternal and offspring cardiovascular disease. However, the etiology and pathogenesis of preeclampsia are complicated and have not been fully elucidated. Obesity, immunological diseases and endocrine metabolic diseases are high-risk factors for the development of preeclampsia. Effective methods to treat preeclampsia are lacking, and termination of pregnancy remains the only curative treatment for preeclampsia. The pathogenesis of preeclampsia include poor placentation, uteroplacental malperfusion, oxidative stress, endoplasmic reticulum stress, dysregulated immune tolerance, vascular inflammation and endothelial cell dysfunction. The notion that placenta is the core factor in the pathogenesis of preeclampsia is still prevailing. G protein-coupled receptors, the largest family of membrane proteins in eukaryotes and the largest drug target family to date, exhibit diversity in structure and function. Among them, the secretin/adhesion (Class B) G protein-coupled receptors are essential drug targets for human diseases, such as endocrine diseases and cardiometabolic diseases. Given the great value of the secretin/adhesion (Class B) G protein-coupled receptors in the regulation of cardiovascular system function and the drug target exploration, we summarize the role of these receptors in placental development and preeclampsia, and outlined the relevant pathological mechanisms, thereby providing potential drug targets for preeclampsia treatment.
子痫前期是一种主要以高血压和蛋白尿为特征的临床综合征，全球发病率为3%-8%，孕产妇死亡率高，是与孕产妇和子代心血管疾病高度相关的危险因素。然而，子痫前期的病因和发病机制复杂，尚未完全阐明。肥胖、免疫性疾病和内分泌代谢疾病是子痫前期发生发展的高危因素。目前缺乏治疗子痫前期的有效方法，终止妊娠仍是子痫前期唯一的治愈性治疗手段。子痫前期的发病机制包括胎盘形成不良、子宫胎盘灌注不足、氧化应激、内质网应激、免疫耐受失调、血管炎症和内皮细胞功能障碍。胎盘是子痫前期发病机制的核心因素这一观点仍然盛行。G蛋白偶联受体是真核生物中最大的膜蛋白家族，也是迄今为止最大的药物靶点家族，其结构和功能具有多样性。其中，分泌素/黏附（B类）G蛋白偶联受体是人类疾病如内分泌疾病和心脏代谢疾病的重要药物靶点。鉴于分泌素/黏附（B类）G蛋白偶联受体在调节心血管系统功能及药物靶点探索方面的巨大价值，我们总结了这些受体在胎盘发育和子痫前期中的作用，并概述了相关病理机制，从而为子痫前期治疗提供潜在的药物靶点。
