Effect of Endothelial Microparticles Induced by Hypoxia on Migration and Angiogenesis of Human Umbilical Vein Endothelial Cells by Delivering MicroRNA-19b
Effect of Endothelial Microparticles Induced by Hypoxia on Migration and Angiogenesis of Human Umbilical Vein Endothelial Cells by Delivering MicroRNA-19b作者机构:Department of CardiologyBeijing Key Laboratory of Early Prediction and Intervention of Acute Myocardial InfarctionCenter for Cardiovascular Translational ResearchPeking University People's HospitalBeijing 100044China
出 版 物:《Chinese Medical Journal》 (中华医学杂志(英文版))
年 卷 期:2018年第131卷第22期
页 面:2726-2733页
核心收录:
基 金:grants from the National Natural Science Foundation of China (Nos.81770356 81470473 and 81600340)and the Capital Health Research and Development of Special (No.2016-2-4083)
主 题:Endothelial Microparticle MicroRNA-19b Hypoxia Cell Migration Angiogenesis Transforming Growth Factor-β2
摘 要:Background: Microparticles (MPs) are small extracellular plasma membrane particles shed by activated and apoptotic cells, which are involved in the development of atherosclerosis. Our previous study found that microRNA (miR)-19b encapsulated within endothelial MPs (EMPs) may contribute to the upregulation of circulating miR-19b in unstable angina patients. Hypoxia is involved in atherosclerosis as a critical pathological stimulus. However, it still remains unclear whether the increase of miR-19b levels in EMPs is related to hypoxia and if the effect of miR-19b - wrapped within EMPs - stimulates hypoxia on vascular endothelial cells. This study aimed to explore the changes of miR-19b in EMPs induced by hypoxia as well as their effects on endothelial ***: Human umbilical vein endothelial cells (HUVECs) were culturedin vitro and arranged to harvest EMPs in two parts: the first part consisted of EMPcontrol and EMPhypoxia and the second part included EMPvehicle, EMPNC mimic, and EMPmiR-19b mimic. Cell migration was detected by scratch migration and transwell chamber migration. Angiogenesis was assessed by tube formation assays. Furthermore, we predicted the target gene of miR-19b by bioinformatics analysis, and luciferase assay was used to verify the targeted gene of miR-19b. Data were analyzed by one-way analysis of variance. Student’st-test was used when two groups were ***: Compared with EMPcontrol- and EMPhypoxia-inhibited migration of cells by scratch migration assay (80.77 ± 1.10 vs. 28.37 ± 1.40,P 0. 001) and transwell chamber migration assay (83.00 ± 3.46 vs. 235.00 ± 16.52,P 0.01), the number of tube formations was markedly reduced by 70% in the EMPhypoxia group (P 0.001)in vitro analysis of HUVECs. Meanwhile, a strong inhibition of migration and tube formation of HUVECs in the presence of miR-19b-enriched EMPmiR-19b mimic was observed. This effect might be due to the delivery of miR-19b in EMPs. Transforming growth factor-β2 (TGFβ2)