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Astragaloside IV (ASIV) Mediates Endothelial Progenitor Cell (EPC) Exosomal <i>LINC01963</i> to Inhibit Pyroptosis and Oxidative Stress in High Glucose-impaired Endothelial Cells

[ Vol. 24 , Issue. 2 ]


Wu Xiong, Xi Zhang*, Jian-da Zhou, Mei-xin Tan, Yu Liu, Yu Yan, Hua-Juan Lei, Jia-rui Peng, Wei Liu and Pei Tan   Pages 252 - 263 ( 12 )


<p>Background: Hyperglycemia is widespread in the world’s population, increasing the risk of many diseases. This study aimed to explore the regulatory effect and mechanism of astragaloside IV (ASIV)-mediated endothelial progenitor cells (EPCs) exosomal <i>LINC01963</i> in endothelial cells (HUVECs) impaired by high glucose. <p> Methods: Morphologies of exosomes were observed by light microscope and electron microscope. Immunofluorescence was used to identify EPCs and detect the expressions of caspase-1. <i>LINC01963</i> was detected by quantitative reverse transcription PCR. NLRP3, ASC, and caspase-3 were detected by Western Blot. Nanoparticle tracking analysis was carried out to analyze the exosome diameter. High-throughput sequencing was applied to screen target lncRNAs. The proliferation of endothelial cells was measured by cell counting kit-8 assay. The apoptosis level of HUVECs was detected by flow cytometry and TdT-mediated dUTP Nick-End labeling. The levels of IL- 1&#946;, IL-18, ROS, SOD, MDA, and LDH were measured by enzyme-linked immunosorbent assay. <p> Results: ASIV could promote the secretion of the EPC exosome. <i>LINC01963</i> was obtained by high-throughput sequencing. It was observed that high glucose could inhibit the proliferation, reduce the level of SOD, the expression of NLRP3, ASC, and caspase- 1, increase the levels of IL-1&#946;, IL-18, ROS, MDA, and LDH, and promote apoptosis of HUVECs. Whereas <i>LINC01963</i> could inhibit the apoptosis of HUVECs, the increase the expression of NLRP3, ASC, and caspase-1, and decrease the levels of IL-1&#946;, IL-18, ROS, MDA, and LDH. <p> Conclusion: EPCs exosomal <i>LINC01963</i> play an inhibitory role in high glucoseinduced pyroptosis and oxidative stress of HUVECs. This study provides new ideas and directions for treating hyperglycemia and researching exosomal lncRNAs.</p>


Astragaloside IV, LINC01963, EPC, exosome, pyroptosis, oxidative stress.


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