Patsouras Markos, Alexopoulou Eirini, Foutadakis Spyros, Tsiki Eirini, Karagianni Panagiota, Agelopoulos Marios, Vlachoyiannopoulos Panayiotis G
Department of Pathophysiology, Medical School, National and Kapodistrian University of Athens, Greece.
Center of Basic Research, Biomedical Research Foundation, Academy of Athens, 4 Soranou Ephessiou Street, Athens, 11527, Greece.
J Transl Autoimmun. 2023 May 2;6:100202. doi: 10.1016/j.jtauto.2023.100202. eCollection 2023.
Antiphospholipid syndrome (APS) is an autoimmune thrombophilia characterized by recurrent thrombotic events and/or pregnancy morbidity in the presence of antiphospholipid antibodies detected either as anti-cardiolipin, anti-β2 Glycoprotein I (anti-β2GPI) or Lupus anticoagulant (LA). Endothelial deregulation characterizes the syndrome. To address gene expression changes accompanying the development of autoimmune phenotype in endothelial cells in the context of APS, we performed analysis in Human Umbilical Vein Endothelial Cells (HUVECs) stimulated with IgG from APS patients and β2GPI, followed by intersection of RNA-seq data with published microarray and ChIP-seq results (Chromatin Immunoprecipitation). Our strategy revealed that during HUVEC activation diverse signaling pathways such as TNF-α, TGF-β, MAPK38, and Hippo are triggered as indicated by Gene Ontology (GO) classification and pathway analysis. Finally, cell biology approaches performed side-by-side in naïve and stimulated cultured HUVECs, as well as, in placenta specimens derived from Healthy donors (HDs) and APS-patients verified the evolution of an APS-characteristic gene expression program in endothelial cells during the initial stages of the disease's development.
抗磷脂综合征（APS）是一种自身免疫性血栓形成倾向疾病，其特征为在检测到抗心磷脂、抗β2糖蛋白I（抗β2GPI）或狼疮抗凝物（LA）等抗磷脂抗体的情况下，出现复发性血栓事件和/或妊娠并发症。内皮细胞功能失调是该综合征的特征。为了研究在APS背景下内皮细胞自身免疫表型发展过程中伴随的基因表达变化，我们对用APS患者的IgG和β2GPI刺激的人脐静脉内皮细胞（HUVECs）进行了分析，然后将RNA测序数据与已发表的微阵列和染色质免疫沉淀测序（ChIP-seq）结果进行交叉分析。我们的策略表明，在HUVEC激活过程中，基因本体（GO）分类和通路分析显示，多种信号通路如肿瘤坏死因子-α（TNF-α）、转化生长因子-β（TGF-β）、丝裂原活化蛋白激酶38（MAPK38）和Hippo信号通路被触发。最后，在未处理和经刺激的培养HUVECs以及来自健康供体（HDs）和APS患者的胎盘标本中并行进行的细胞生物学方法，证实了在疾病发展的初始阶段内皮细胞中APS特征性基因表达程序的演变。
