Gajić Maja, Schröder-Heurich Bianca, Mayer-Pickel Karoline
Department of Obstetrics and Gynecology, Medical University of Graz, Graz, Austria.
Gynecology Research Unit, Hannover Medical School, Hannover, Germany.
Front Pharmacol. 2024 Feb 5;15:1298928. doi: 10.3389/fphar.2024.1298928. eCollection 2024.
Preeclampsia (PE) is a complex pregnancy-related disorder characterized by hypertension, followed by organ dysfunction and uteroplacental abnormalities. It remains a major cause of maternal and neonatal morbidity and mortality worldwide. Although the pathophysiology of PE has not been fully elucidated, a two-stage model has been proposed. In this model, a poorly perfused placenta releases various factors into the maternal circulation during the first stage, including pro-inflammatory cytokines, anti-angiogenic factors, and damage-associated molecular patterns into the maternal circulation. In the second stage, these factors lead to a systemic vascular dysfunction with consecutive clinical maternal and/or fetal manifestations. Despite advances in feto-maternal management, effective prophylactic and therapeutic options for PE are still lacking. Since termination of pregnancy is the only curative therapy, regardless of gestational age, new treatment/prophylactic options are urgently needed. Hydroxychloroquine (HCQ) is mainly used to treat malaria as well as certain autoimmune conditions such as systemic lupus and rheumatoid arthritis. The exact mechanism of action of HCQ is not fully understood, but several mechanisms of action have been proposed based on its pharmacological properties. Interestingly, many of them might counteract the proposed processes involved in the development of PE. Therefore, based on a literature review, we aimed to investigate the interrelated biological processes of HCQ and PE and to identify potential molecular targets in these processes.
子痫前期（PE）是一种与妊娠相关的复杂疾病，其特征为高血压，随后出现器官功能障碍和子宫胎盘异常。它仍是全球孕产妇和新生儿发病及死亡的主要原因。尽管PE的病理生理学尚未完全阐明，但已提出了一个两阶段模型。在该模型中，胎盘灌注不良在第一阶段会向母体循环中释放多种因子，包括促炎细胞因子、抗血管生成因子以及损伤相关分子模式进入母体循环。在第二阶段，这些因子会导致全身血管功能障碍，并伴有连续的母体和/或胎儿临床症状。尽管在母婴管理方面取得了进展，但仍缺乏针对PE的有效预防和治疗方案。由于终止妊娠是唯一的治愈性疗法，无论孕周如何，迫切需要新的治疗/预防方案。羟氯喹（HCQ）主要用于治疗疟疾以及某些自身免疫性疾病，如系统性红斑狼疮和类风湿性关节炎。HCQ的确切作用机制尚未完全了解，但基于其药理特性已提出了几种作用机制。有趣的是，其中许多机制可能会抵消PE发生过程中所涉及的拟议过程。因此，基于文献综述，我们旨在研究HCQ与PE的相关生物学过程，并确定这些过程中的潜在分子靶点。
