Clinical Research Branch, Instituto Nacional de Perinatología Isidro Espinosa de los Reyes, Mexico City 11000, Mexico.
Obstetric and Gynecology Department, Hospital General de México Dr. Eduardo Liceaga, Mexico City 06720, Mexico.
Int J Mol Sci. 2024 Jul 10;25(14):7569. doi: 10.3390/ijms25147569.
Preeclampsia (PE) is a multifactorial pregnancy disorder characterized by hypertension and proteinuria, posing significant risks to both maternal and fetal health. Despite extensive research, its complex pathophysiology remains incompletely understood. This narrative review aims to elucidate the intricate mechanisms contributing to PE, focusing on abnormal placentation, maternal systemic response, oxidative stress, inflammation, and genetic and epigenetic factors. This review synthesizes findings from recent studies, clinical trials, and meta-analyses, highlighting key molecular and cellular pathways involved in PE. The review integrates data on oxidative stress biomarkers, angiogenic factors, immune interactions, and mitochondrial dysfunction. PE is initiated by poor placentation due to inadequate trophoblast invasion and improper spiral artery remodeling, leading to placental hypoxia. This triggers the release of anti-angiogenic factors such as soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng), causing widespread endothelial dysfunction and systemic inflammation. Oxidative stress, mitochondrial abnormalities, and immune dysregulation further exacerbate the condition. Genetic and epigenetic modifications, including polymorphisms in the Fms-like tyrosine kinase 1 (FLT1) gene and altered microRNA (miRNA) expression, play critical roles. Emerging therapeutic strategies targeting oxidative stress, inflammation, angiogenesis, and specific molecular pathways like the heme oxygenase-1/carbon monoxide (HO-1/CO) and cystathionine gamma-lyase/hydrogen sulfide (CSE/H2S) pathways show promise in mitigating preeclampsia's effects. PE is a complex disorder with multifactorial origins involving abnormal placentation, endothelial dysfunction, systemic inflammation, and oxidative stress. Despite advances in understanding its pathophysiology, effective prevention and treatment strategies remain limited. Continued research is essential to develop targeted therapies that can improve outcomes for both mothers and their babies.
子痫前期 (PE) 是一种多因素的妊娠疾病，其特征为高血压和蛋白尿，对母婴健康均构成重大威胁。尽管已有大量研究，但它的复杂病理生理学仍未被完全理解。本综述旨在阐明导致 PE 的复杂机制，重点关注异常胎盘形成、母体全身反应、氧化应激、炎症以及遗传和表观遗传因素。本综述综合了来自近期研究、临床试验和荟萃分析的发现，重点介绍了与 PE 相关的关键分子和细胞途径。综述整合了氧化应激生物标志物、血管生成因子、免疫相互作用和线粒体功能障碍的数据。PE 是由于滋养细胞侵袭不足和螺旋动脉重塑不当导致胎盘缺氧而引发的，这是由不良的胎盘形成引起的。这会触发抗血管生成因子（如可溶性 fms 样酪氨酸激酶-1 (sFlt-1) 和可溶性内皮糖蛋白 (sEng)）的释放，导致广泛的内皮功能障碍和全身炎症。氧化应激、线粒体异常和免疫失调进一步加重了病情。遗传和表观遗传修饰，包括 Fms 样酪氨酸激酶 1 (FLT1) 基因的多态性和改变的 microRNA (miRNA) 表达，也起着关键作用。针对氧化应激、炎症、血管生成以及特定分子途径（如血红素加氧酶-1/一氧化碳 (HO-1/CO) 和半胱氨酸γ-裂解酶/硫化氢 (CSE/H2S) 途径）的新兴治疗策略在减轻 PE 的影响方面显示出了希望。PE 是一种具有多因素起源的复杂疾病，涉及异常胎盘形成、内皮功能障碍、全身炎症和氧化应激。尽管在理解其病理生理学方面取得了进展，但有效的预防和治疗策略仍然有限。继续开展研究对于开发靶向治疗方法以改善母婴结局至关重要。
