Dong Yan, Lu Yuan, Xia Yu, Wang Xietong
Department of Obstetrics and Gynaecology,Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
Department of obstetrics and Gynaecology, Linyi People's Hospital, Linyi, Shandong, China.
J Matern Fetal Neonatal Med. 2022 Dec;35(25):7084-7092. doi: 10.1080/14767058.2021.1943656. Epub 2021 Jun 28.
Antiphospholipid syndrome (APS) is an autoimmune disease characterized by thrombotic events and/or pregnancy morbidity (≥3 recurrent early miscarriage or fetal death or a prematurity <34 weeks of gestation) with persistently positive antiphospholipid antibodies (aPLs). It is reported that aPLs damage the placental tissue by binding to β2-glycoprotein I (β2GPI) on the surface of trophoblast and endothelial cells. Hydroxychloroquine (HCQ) is considered to be beneficial in the treatment of obstetrical APS and shown to restore the aPL-inhibited invasion and differentiation of trophoblast. However, not enough evidence exists regarding the effect of HCQ on endometrial angiogenesis. The aim of our study was to assess whether HCQ has an effect on aPL-inhibited endothelial angiogenesis.
In this research, to explore the effect of HCQ for angiogenesis, we investigated: (1) Human umbilical vein endothelial cells (HUVECs) viability by CCK-8; (2) HUVECs migration by wound healing; (3) HUVEC angiogenesis by Matrigel assay ; (4) mRNA expression of and by real-time quantitative Polymerase Chain Reaction (RT-PCR); (5) protein expression of VEGF, MMP-2 by western blot.
We found that HCQ treatment significantly restored the expression of aPL-inhibited and . HCQ restored aPL-inhibited HUVEC proliferation, migration, and angiogenesis .
In conclusion, aPLs inhibit HUVECs angiogenesis, however, HCQ can restore the effect of aPL-inhibited HUVECs migration and angiogenesis , demonstrating its beneficial therapeutic role in obstetrical APS.
抗磷脂综合征（APS）是一种自身免疫性疾病，其特征为血栓形成事件和/或妊娠并发症（≥3次反复早期流产或胎儿死亡或孕周<34周的早产），且抗磷脂抗体（aPLs）持续呈阳性。据报道，aPLs通过与滋养层细胞和内皮细胞表面的β2糖蛋白I（β2GPI）结合来损伤胎盘组织。羟氯喹（HCQ）被认为对产科APS的治疗有益，并已显示可恢复aPL抑制的滋养层细胞侵袭和分化。然而，关于HCQ对子宫内膜血管生成的影响，现有证据不足。我们研究的目的是评估HCQ是否对aPL抑制的内皮血管生成有影响。
在本研究中，为探究HCQ对血管生成的影响，我们进行了以下研究：（1）通过CCK-8检测人脐静脉内皮细胞（HUVECs）的活力；（2）通过伤口愈合实验检测HUVECs的迁移；（3）通过基质胶实验检测HUVECs的血管生成；（4）通过实时定量聚合酶链反应（RT-PCR）检测 和 的mRNA表达；（5）通过蛋白质印迹法检测血管内皮生长因子（VEGF）、基质金属蛋白酶-2（MMP-2）的蛋白表达。
我们发现，HCQ治疗显著恢复了aPL抑制的 和 的表达。HCQ恢复了aPL抑制的HUVECs增殖、迁移和血管生成。
总之，aPLs抑制HUVECs血管生成，然而，HCQ可恢复aPL抑制的HUVECs迁移和血管生成的作用，证明其在产科APS中具有有益的治疗作用。
