Arraystar human lncRNA microarray V3.0

Preeclampsia (PE) is a peculiar multisystemic disorder that contributes to maternal and perinatal morbidity. Exosomes, existing in the circulation, origin from late endosomes which are secreted into the extracellular surrounding by diverse cell types under different conditions, can mediate intercellular communication via transporting its constituents and regulate inflammation, immunomodulation and angiogenesis. We hypothesize that exosomes from trophoblast in preeclampsia complications under pathological hypoxia microenvironment impair vascular development by transmitting its contents to endothelial cells. Here, transwell and tube formation assays revealed that exosomes from hypoxic trophoblast cells attenuated the migration, and tube formation in human umbilical vein endothelial cells (HUVECs) in vitro. In a mouse model, hypoxic trophoblast cells derived exosomes leaded to vascular dysfunction and caused adverse PE-like birth outcomes. Next, we detected lncRNA expression in cord blood plasma derived exosomes from gestational age-matched preeclampsia and normal pregnancies by microarray analysis. Then, we identified the possible mechanisms of one up-regulated exosomal lncRNA, TINCR. Application of Quantitative RT-PCR, lncTINCR was confirmed overexpressing in exosomes released from cord blood plasma, peripheral blood plasma and human placental trophoblasts of preeclampsia patients. Moreover, the exosomal lncTINCR could be specifically secreted by hypoxic trophoblast cells and transferred to HUVECs, which increased autophagy in HUVECs and impaired angiogenesis of endothelial cells in vitro. Furthermore, we demonstrated that lncTINCR was considered as a competing endogenous RNA to regulate miR-424, which resulted in elevated ATG5 expression. Thus, we reported that exosomes intervened effective delivering of lncTINCR to endothelial cells to damage vascular functions and result in the development of PE. The newly identified exosomal lncTINCR /miR-424/ATG5 axis may present potential novel targets of diagnosis and treatment for PE. lncRNA profiles of cord blood plasma derived exosomes from gestational age-matched preeclampsia and normal pregnancies Xiang,Ying