{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T22:29:58Z","timestamp":1790720998465,"version":"4.1.0"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,5,9]],"date-time":"2022-05-09T00:00:00Z","timestamp":1652054400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Bioeng. Biotechnol."],"abstract":"<jats:p>\n                    Endothelial dysfunction is a key accessory to diabetic cardiovascular complications, and the regulatory role of the extracellular vesicles (EVs) from the innate immune system is growing. We tested whether EVs derived from high glucose-induced monocytes could shuttle microRNAs and impair endothelial cells. EVs from high glucose- and basal glucose-treated THP-1 cells (\n                    <jats:sup>HG-<\/jats:sup>\n                    THP-1 EVs and\n                    <jats:sup>BG-<\/jats:sup>\n                    THP-1 EVs) were isolated and identified. After coculture with THP-1 EVs, human umbilical vein endothelial cells (HUVECs) were tested by proliferation, migration, reactive oxygen species (ROS) detection assays, and western blot for Nrf2\/NLRP3 signaling. MiR-142-5p was predicted by miRNAs databases and further verified by RT\u2013qPCR and dual-luciferase reporter gene assays that inhibit Nrf2 expression. The regulation of miR-142-5p in HUVECs was further evaluated. A type 1 diabetes mellitus (T1DM) mouse model was developed for miR-142-5p inhibition. Aorta tissue was harvested for hematoxylin-eosin staining and immunohistochemistry of interleukin-1\u03b2 (IL-1\u03b2). Compared to\n                    <jats:sup>BG-<\/jats:sup>\n                    THP-1 EVs,\n                    <jats:sup>HG-<\/jats:sup>\n                    THP-1 EVs significantly reduced migration and increased ROS production in HUVECs but did not affect proliferation.\n                    <jats:sup>HG-<\/jats:sup>\n                    THP-1 EVs induced suppression of Nrf2 signaling and NLRP3 signaling activation. RT\u2013qPCR results showed that\n                    <jats:sup>HG-<\/jats:sup>\n                    THP-1 EVs overexpressed miR-142-5p in HUVECs. The transfection of miR-142-5p mimics into HUVECs exhibited consistent regulatory effects on\n                    <jats:sup>HG-<\/jats:sup>\n                    THP-1 EVs, whereas miR-142-5p inhibitors demonstrated protective effects. The miR-142-5p antagomir significantly reduced the IL-1\u03b2 level in T1DM aortas despite morphological changes. To conclude, miR-142-5p transferred by high glucose-induced monocyte EVs participates in diabetic endothelial damage. The inhibition of miR-142-5p could be a potential adjuvant to diabetic cardiovascular protection.\n                  <\/jats:p>","DOI":"10.3389\/fbioe.2022.913791","type":"journal-article","created":{"date-parts":[[2022,5,9]],"date-time":"2022-05-09T02:44:43Z","timestamp":1652064283000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":16,"title":["A Potential Target for Diabetic Vascular Damage: High Glucose-Induced Monocyte Extracellular Vesicles Impair Endothelial Cells by Delivering miR-142-5p"],"prefix":"10.3389","volume":"10","author":[{"given":"Rui","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Niu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihua","family":"Rong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengshi","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leng","family":"Ni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Di","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changwei","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,5,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1677","DOI":"10.1007\/s12011-021-02773-4","article-title":"The Prospective Ameliorative Role of Zinc Oxide Nanoparticles in STZ-Induced Diabetic Nephropathy in Rats: Mechanistic Targeting of Autophagy and Regulating Nrf2\/TXNIP\/NLRP3 Inflammasome Signaling","volume":"200","author":"Abd El-Khalik","year":"2021","journal-title":"Biol. Trace Elem. Res."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1463","DOI":"10.3390\/antiox10091463","article-title":"Nrf2 and Heme Oxygenase-1 Involvement in Atherosclerosis Related Oxidative Stress","volume":"10","author":"Alonso-Pi\u00f1eiro","year":"2021","journal-title":"Antioxidants"},{"key":"B3","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1186\/1471-2105-15-293","article-title":"Jvenn: an Interactive Venn Diagram Viewer","volume":"15","author":"Bardou","year":"2014","journal-title":"BMC Bioinforma."},{"key":"B4","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1016\/s0092-8674(04)00045-5","article-title":"MicroRNAs","volume":"116","author":"Bartel","year":"2004","journal-title":"Cell"},{"key":"B5","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1101\/gr.082701.108","article-title":"Most Mammalian mRNAs Are Conserved Targets of microRNAs","volume":"19","author":"Friedman","year":"2009","journal-title":"Genome Res."},{"key":"B6","doi-asserted-by":"publisher","first-page":"682948","DOI":"10.3389\/fimmu.2021.682948","article-title":"Extracellular Vesicles in Immune System Regulation and Type 1 Diabetes: Cell-To-Cell Communication Mediators, Disease Biomarkers, and Promising Therapeutic Tools","volume":"12","author":"Grieco","year":"2021","journal-title":"Front. Immunol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"3521","DOI":"10.1093\/eurheartj\/ehx581","article-title":"Monocyte and Haematopoietic Progenitor Reprogramming as Common Mechanism Underlying Chronic Inflammatory and Cardiovascular Diseases","volume":"39","author":"Hoogeveen","year":"2018","journal-title":"Eur. Heart J."},{"key":"B8","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/j.bbrc.2021.08.053","article-title":"Exosomal Long Non-coding RNA LIPCAR Derived from oxLDL-Treated THP-1 Cells Regulates the Proliferation of Human Umbilical Vein Endothelial Cells and Human Vascular Smooth Muscle Cells","volume":"575","author":"Hu","year":"2021","journal-title":"Biochem. Biophysical Res. Commun."},{"key":"B9","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1002\/biof.1395","article-title":"Dihydromyricetin Inhibits NLRP3 Inflammasome-dependent Pyroptosis by Activating the Nrf2 Signaling Pathway in Vascular Endothelial Cells","volume":"44","author":"Hu","year":"2018","journal-title":"Biofactors"},{"key":"B10","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.atherosclerosis.2010.01.035","article-title":"Protective Effects of Magnesium Lithospermate B against Diabetic Atherosclerosis via Nrf2-ARE-NQO1 Transcriptional Pathway","volume":"211","author":"Hur","year":"2010","journal-title":"Atherosclerosis"},{"key":"B11","doi-asserted-by":"publisher","first-page":"187","DOI":"10.3892\/ijmm.2021.5020","article-title":"Oxymatrine Attenuates Oxidized Low-density L-ipoprotein-induced HUVEC I-njury by I-nhibiting NLRP3 I-nflammasome-mediated P-yroptosis via the A-ctivation of the SIRT1\/Nrf2 S-ignaling P-athway","volume":"48","author":"Jin","year":"2021","journal-title":"Int. J. Mol. Med."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1476","DOI":"10.14336\/AD.2021.0708","article-title":"Therapeutic Potential of Nucleic Acids when Combined with Extracellular Vesicles","volume":"12","author":"Jurgielewicz","year":"2021","journal-title":"Aging Dis."},{"key":"B13","doi-asserted-by":"publisher","first-page":"D239","DOI":"10.1093\/nar\/gkx1141","article-title":"DIANA-TarBase V8: a Decade-Long Collection of Experimentally Supported miRNA-Gene Interactions","volume":"46","author":"Karagkouni","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"B14","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1038\/ng1536","article-title":"Combinatorial microRNA Target Predictions","volume":"37","author":"Krek","year":"2005","journal-title":"Nat. Genet."},{"key":"B15","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1007\/s11010-017-3256-x","article-title":"Fenofibrate Ameliorates Diabetic Retinopathy by Modulating Nrf2 Signaling and NLRP3 Inflammasome Activation","volume":"445","author":"Liu","year":"2018","journal-title":"Mol. Cell Biochem."},{"key":"B16","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1186\/s13059-019-1629-z","article-title":"Prediction of Functional microRNA Targets by Integrative Modeling of microRNA Binding and Target Expression Data","volume":"20","author":"Liu","year":"2019","journal-title":"Genome Biol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"205873842090904","DOI":"10.1177\/2058738420909041","article-title":"miR-142-5p Regulates the Progression of Diabetic Retinopathy by Targeting IGF1","volume":"34","author":"Liu","year":"2020","journal-title":"Int. J. Immunopathol. Pharmacol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"65","DOI":"10.3727\/096504016X14719078133366","article-title":"MicroRNA-142-5p Overexpression Inhibits Cell Growth and Induces Apoptosis by Regulating FOXO in Hepatocellular Carcinoma Cells","volume":"25","author":"Lou","year":"2017","journal-title":"Oncol. Res."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1306","DOI":"10.3390\/antiox10081306","article-title":"Pathophysiological Association between Diabetes Mellitus and Endothelial Dysfunction","volume":"10","author":"Maruhashi","year":"2021","journal-title":"Antioxidants"},{"key":"B20","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2013\/879516","article-title":"Therapeutic Effect of MG132 on the Aortic Oxidative Damage and Inflammatory Response in OVE26 Type 1 Diabetic Mice","volume":"2013","author":"Miao","year":"2013","journal-title":"Oxidative Med. Cell. Longev."},{"key":"B21","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1186\/s12872-021-01893-y","article-title":"Circulating Level of microRNA-142-5p Is a Potential Biomarker for Predicting In-Stent Restenosis: a Case-Control Study","volume":"21","author":"Pan","year":"2021","journal-title":"BMC Cardiovasc Disord."},{"key":"B22","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1161\/CIRCRESAHA.118.314601","article-title":"Mitochondria Are a Subset of Extracellular Vesicles Released by Activated Monocytes and Induce Type I IFN and TNF Responses in Endothelial Cells","volume":"125","author":"Puhm","year":"2019","journal-title":"Circ. Res."},{"key":"B23","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1016\/j.imbio.2019.02.004","article-title":"Exosomes Derived from Monocytes and from Endothelial Cells Mediate Monocyte and Endothelial Cell Activation under High D-Glucose Conditions","volume":"224","author":"S\u00e1ez","year":"2019","journal-title":"Immunobiology"},{"key":"B24","doi-asserted-by":"publisher","first-page":"2663","DOI":"10.3390\/cells10102663","article-title":"Role of Extracellular Vesicles in Cell Death and Inflammation","volume":"10","author":"Sanwlani","year":"2021","journal-title":"Cells"},{"key":"B25","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1186\/s12933-017-0513-y","article-title":"The Nuclear Factor (Erythroid-derived 2)-like 2 (Nrf2) Activator Dh404 Protects against Diabetes-Induced Endothelial Dysfunction","volume":"16","author":"Sharma","year":"2017","journal-title":"Cardiovasc Diabetol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"824165","DOI":"10.3389\/fcell.2022.824165","article-title":"The Molecular Pathways of Pyroptosis in Atherosclerosis","volume":"10","author":"Song","year":"2022","journal-title":"Front. Cell Dev. Biol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1857","DOI":"10.3389\/fphys.2018.01857","article-title":"Therapeutic Options Targeting Oxidative Stress, Mitochondrial Dysfunction and Inflammation to Hinder the Progression of Vascular Complications of Diabetes","volume":"9","author":"Teodoro","year":"2018","journal-title":"Front. Physiol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1042\/CS20180905","article-title":"Trained Immunity and Diabetic Vascular Disease","volume":"133","author":"Thiem","year":"2019","journal-title":"Clin. Sci. (Lond)"},{"key":"B29","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1016\/j.bbrc.2021.02.070","article-title":"Melatonin Attenuates Restenosis after Vascular Injury in Diabetic Rats through Activation of the Nrf2 Signaling Pathway","volume":"548","author":"Wang","year":"2021","journal-title":"Biochem. Biophysical Res. Commun."},{"key":"B30","doi-asserted-by":"publisher","first-page":"733985","DOI":"10.3389\/fcvm.2021.733985","article-title":"Mechanisms of Action of MiRNAs and LncRNAs in Extracellular Vesicle in Atherosclerosis","volume":"8","author":"Xu","year":"2021","journal-title":"Front. Cardiovasc. Med."},{"key":"B31","doi-asserted-by":"publisher","first-page":"3229","DOI":"10.3892\/mmr.2015.3191","article-title":"Upregulation of miR-142-5p in Atherosclerotic Plaques and Regulation of Oxidized Low-Density Lipoprotein-Induced Apoptosis in Macrophages","volume":"11","author":"Xu","year":"2015","journal-title":"Mol. Med. Rep."},{"key":"B32","doi-asserted-by":"publisher","first-page":"105868","DOI":"10.1016\/j.phrs.2021.105868","article-title":"Targeting the microRNAs in Exosome: A Potential Therapeutic Strategy for Alleviation of Diabetes-Related Cardiovascular Complication","volume":"173","author":"Zhao","year":"","journal-title":"Pharmacol. Res."},{"key":"B33","doi-asserted-by":"publisher","first-page":"11363","DOI":"10.18632\/aging.202829","article-title":"Melatonin Attenuates Smoking-Induced Atherosclerosis by Activating the Nrf2 Pathway via NLRP3 Inflammasomes in Endothelial Cells","volume":"13","author":"Zhao","year":"","journal-title":"Aging"}],"container-title":["Frontiers in Bioengineering and Biotechnology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fbioe.2022.913791\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,9]],"date-time":"2022-05-09T02:44:46Z","timestamp":1652064286000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fbioe.2022.913791\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,9]]},"references-count":33,"alternative-id":["10.3389\/fbioe.2022.913791"],"URL":"https:\/\/doi.org\/10.3389\/fbioe.2022.913791","relation":{},"ISSN":["2296-4185"],"issn-type":[{"value":"2296-4185","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,9]]},"article-number":"913791"}}