Abstract：
Preeclampsia (PE) is usually associated with the accumulation of reactive oxygen species (ROS) resulting from heightened oxidative stress (OS). Ferroptosis is a unique type of lipid peroxidation-induced iron-dependent cell death distinct from traditional apoptosis, necroptosis, and pyroptosis and most likely contributes considerable to PE pathogenesis. At approximately 10-12 weeks of gestation, trophoblasts create an environment rich in oxygen and iron. In patients with PE, ferroptosis-related genes such as HIF1 and MAPK8 are downregulated, whereas PLIN2 is upregulated. Furthermore, miR-30b-5p overexpression inhibits solute carrier family 11 member 2, resulting in a decrease in glutathione levels and an increase in the labile iron pool. At the maternal-fetal interface, physiological hypoxia/reperfusion and excessive iron result in lipid peroxidation and ROS production. Owing to the high expression of Fpn and polyunsaturated fatty acid-containing phospholipid-related enzymes, including acyl-CoA synthetase long-chain family member 4, lysophosphatidylcholine acyl-transferase 3, and spermidine/spermine N1-acetyltransferase 1, trophoblasts become more susceptible to OS and ROS damage. In stage 1, the injured trophoblasts exhibit poor invasion and incomplete uterine spiral artery remodeling caused by ferroptosis, leading to placental ischemia and hypoxia. Subsequently, ferroptosis marked by OS occurs in stage 2, eventually causing PE. We aimed to explore the new therapeutic target of PE through OS in ferroptosis.
摘要：
先兆子痫（PE）通常与氧化应激（OS）升高导致的活性氧（ROS）的积累有关。Ferroptosis是一种独特的脂质过氧化诱导的铁依赖性细胞死亡，不同于传统的细胞凋亡。坏死,和焦亡，很可能对PE的发病机理有很大贡献。在妊娠大约10-12周，滋养细胞创造了富含氧气和铁的环境。在PE患者中，铁凋亡相关基因如HIF1和MAPK8下调，而PLIN2上调。此外，miR-30b-5p过表达抑制溶质载体家族11成员2，导致谷胱甘肽水平降低和不稳定铁库增加。在母胎界面,生理缺氧/再灌注和过量的铁导致脂质过氧化和ROS产生。由于高表达Fpn和含多不饱和脂肪酸的磷脂相关酶,包括酰基辅酶A合成酶长链家族成员4，溶血磷脂酰胆碱酰基转移酶3和亚精胺/精胺N1-乙酰转移酶1，滋养层变得更容易受到OS和ROS损伤。在第1阶段，受损的滋养细胞表现出弱的侵袭性和铁沉积引起的子宫螺旋动脉不完全重塑，导致胎盘缺血缺氧。随后，OS标记的铁中毒发生在第2阶段，最终导致PE。我们旨在通过OS探索铁凋亡中PE的新治疗靶点。
