{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:53:22Z","timestamp":1792803202662,"version":"4.5.0"},"reference-count":187,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2020,12,21]],"date-time":"2020-12-21T00:00:00Z","timestamp":1608508800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Vascular calcification (VC) is a cardiovascular complication associated with a high mortality rate, especially in patients with diabetes, atherosclerosis or chronic kidney disease (CKD). In CKD patients, VC is associated with the accumulation of uremic toxins, such as indoxyl sulphate or inorganic phosphate, which can have a major impact in vascular remodeling. During VC, vascular smooth muscle cells (VSMCs) undergo an osteogenic switch and secrete extracellular vesicles (EVs) that are heterogeneous in terms of their origin and composition. Under physiological conditions, EVs are involved in cell-cell communication and the maintenance of cellular homeostasis. They contain high levels of calcification inhibitors, such as fetuin-A and matrix Gla protein. Under pathological conditions (and particularly in the presence of uremic toxins), the secreted EVs acquire a pro-calcifying profile and thereby act as nucleating foci for the crystallization of hydroxyapatite and the propagation of calcification. Here, we review the most recent findings on the EVs\u2019 pathophysiological role in VC, the impact of uremic toxins on EV biogenesis and functions, the use of EVs as diagnostic biomarkers and the EVs\u2019 therapeutic potential in CKD.<\/jats:p>","DOI":"10.3390\/toxins12120811","type":"journal-article","created":{"date-parts":[[2020,12,21]],"date-time":"2020-12-21T09:41:41Z","timestamp":1608543701000},"page":"811","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Effects of Chronic Kidney Disease and Uremic Toxins on Extracellular Vesicle Biology"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6849-7098","authenticated-orcid":false,"given":"Linda","family":"Yaker","sequence":"first","affiliation":[{"name":"MP3CV-UR7517, CURS-Universit\u00e9 de Picardie Jules Verne, Avenue de la Croix Jourdain, F-80054 Amiens, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sa\u00efd","family":"Kamel","sequence":"additional","affiliation":[{"name":"MP3CV-UR7517, CURS-Universit\u00e9 de Picardie Jules Verne, Avenue de la Croix Jourdain, F-80054 Amiens, France"},{"name":"Laboratoire de Biochimie CHU Amiens-Picardie, Avenue de la Croix Jourdain, F-80054 Amiens, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3059-9777","authenticated-orcid":false,"given":"J\u00e9r\u00f4me","family":"Ausseil","sequence":"additional","affiliation":[{"name":"INSERM UMR1043, CNRS UMR5282, University of Toulouse III, F-31024 Toulouse, France"},{"name":"CHU PURPAN\u2014Institut F\u00e9d\u00e9ratif de Biologie, Laboratoire de Biochimie, Avenue de Grande Bretagne, F-31059 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agn\u00e8s","family":"Boullier","sequence":"additional","affiliation":[{"name":"MP3CV-UR7517, CURS-Universit\u00e9 de Picardie Jules Verne, Avenue de la Croix Jourdain, F-80054 Amiens, France"},{"name":"Laboratoire de Biochimie CHU Amiens-Picardie, Avenue de la Croix Jourdain, F-80054 Amiens, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1038\/nrm.2017.125","article-title":"Shedding light on the cell biology of extracellular vesicles","volume":"19","author":"Raposo","year":"2018","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1038\/nrneph.2017.98","article-title":"Extracellular vesicles in renal disease","volume":"13","author":"Karpman","year":"2017","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1681\/ASN.2015010074","article-title":"Extracellular Vesicles in Renal Diseases: More than Novel Biomarkers?","volume":"27","author":"Le","year":"2016","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Hill, N.R., Fatoba, S.T., Oke, J.L., Hirst, J.A., O\u2019Callaghan, C.A., Lasserson, D.S., and Hobbs, F.D.R. (2016). Global Prevalence of Chronic Kidney Disease\u2014A Systematic Review and Meta-Analysis. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0158765"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1053\/j.ajkd.2014.01.416","article-title":"KDOQI US Commentary on the 2012 KDIGO Clinical Practice Guideline for the Evaluation and Management of CKD","volume":"63","author":"Inker","year":"2014","journal-title":"Am. J. Kidney Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1038\/kisup.2013.79","article-title":"Risk factors for chronic kidney disease: An update","volume":"3","year":"2013","journal-title":"Kidney Int. Suppl."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"5829","DOI":"10.2174\/1381612820666140212194926","article-title":"Vascular Calcification in Chronic Kidney Disease: Role of Disordered Mineral Metabolism","volume":"20","author":"Palit","year":"2014","journal-title":"Curr. Pharm. Des."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Himmelsbach, A., Ciliox, C., and Goettsch, C. (2020). Cardiovascular Calcification in Chronic Kidney Disease\u2014Therapeutic Opportunities. Toxins, 12.","DOI":"10.3390\/toxins12030181"},{"key":"ref_9","first-page":"398","article-title":"Targeting Vascular Calcification in Chronic Kidney Disease","volume":"5","author":"Nelson","year":"2020","journal-title":"JACC Basic Trans. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"167","DOI":"10.2147\/VHRM.S242685","article-title":"Vascular Calcification: An Important Understanding in Nephrology","volume":"16","author":"Mostafavi","year":"2020","journal-title":"Vasc. Health Risk Manag."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"H\u00e9naut, L., Mary, A., Chillon, J.-M., Kamel, S., and Massy, Z.A. (2018). The Impact of Uremic Toxins on Vascular Smooth Muscle Cell Function. Toxins, 10.","DOI":"10.3390\/toxins10060218"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Kalra, H., Drummen, G.P.C., and Mathivanan, S. (2016). Focus on Extracellular Vesicles: Introducing the Next Small Big Thing. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17020170"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1007\/s00018-017-2595-9","article-title":"Current knowledge on exosome biogenesis and release","volume":"75","author":"Hessvik","year":"2018","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Liu, Y., Liu, H., and Tang, W.H. (2019). Exosomes: Biogenesis, biologic function and clinical potential. Cell Biosci., 9.","DOI":"10.1186\/s13578-019-0282-2"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1126\/science.1092425","article-title":"Role of LBPA and Alix in Multivesicular Liposome Formation and Endosome Organization","volume":"303","author":"Matsuo","year":"2004","journal-title":"Science"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1152\/physiol.00029.2004","article-title":"Membrane Microparticles: Two Sides of the Coin","volume":"20","author":"Hugel","year":"2005","journal-title":"Physiology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1146\/annurev-cellbio-101512-122326","article-title":"Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles","volume":"30","author":"Colombo","year":"2014","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1038\/cdd.2010.184","article-title":"Diacylglycerol kinase \u03b1 regulates the formation and polarisation of mature multivesicular bodies involved in the secretion of Fas ligand-containing exosomes in T lymphocytes","volume":"18","author":"Alonso","year":"2011","journal-title":"Cell Death Differ."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1643","DOI":"10.1111\/j.1600-0854.2006.00503.x","article-title":"Citron Kinase, a RhoA Effector, Enhances HIV-1 Virion Production by Modulating Exocytosis","volume":"7","author":"Loomis","year":"2006","journal-title":"Traffic"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1083\/jcb.200511072","article-title":"The V0-ATPase mediates apical secretion of exosomes containing Hedgehog-related proteins in Caenorhabditis elegans","volume":"173","author":"Benedetto","year":"2006","journal-title":"J. Cell Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/j.ceb.2009.03.007","article-title":"Exosomes\u2014Vesicular carriers for intercellular communication","volume":"21","author":"Simons","year":"2009","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3257","DOI":"10.1182\/blood-2004-03-0824","article-title":"Endocytosis, intracellular sorting, and processing of exosomes by dendritic cells","volume":"104","author":"Morelli","year":"2004","journal-title":"Blood"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Groot, M., and Lee, H. (2020). Sorting Mechanisms for MicroRNAs into Extracellular Vesicles and Their Associated Diseases. Cells, 9.","DOI":"10.3390\/cells9041044"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Mulcahy, L.A., Pink, R.C., and Carter, D.R.F. (2014). Routes and mechanisms of extracellular vesicle uptake. J. Extracell. Vesicles, 3.","DOI":"10.3402\/jev.v3.24641"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2037","DOI":"10.1194\/jlr.R084640","article-title":"Extracellular vesicles and their content in bioactive lipid mediators: More than a sack of microRNA","volume":"59","author":"Boilard","year":"2018","journal-title":"J. Lipid Res."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Mir, B., and Goettsch, C. (2020). Extracellular Vesicles as Delivery Vehicles of Specific Cellular Cargo. Cells, 9.","DOI":"10.3390\/cells9071601"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"27066","DOI":"10.3402\/jev.v4.27066","article-title":"Biological properties of extracellular vesicles and their physiological functions","volume":"4","author":"Siljander","year":"2015","journal-title":"J. Extracell. Vesicles"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1658","DOI":"10.1161\/CIRCRESAHA.117.309681","article-title":"Extracellular Vesicles in Angiogenesis","volume":"120","author":"Todorova","year":"2017","journal-title":"Circ. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"8973","DOI":"10.1038\/s41598-018-27190-x","article-title":"A System of Cytokines Encapsulated in ExtraCellular Vesicles","volume":"8","author":"Fitzgerald","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.cytogfr.2019.12.003","article-title":"An emerging interplay between extracellular vesicles and cytokines","volume":"51","author":"Aiello","year":"2020","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2188","DOI":"10.3389\/fimmu.2018.02188","article-title":"From Inflammasome to Exosome\u2014Does Extracellular Vesicle Secretion Constitute an Inflammasome-Dependent Immune Response?","volume":"9","author":"Cypryk","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.blre.2012.12.002","article-title":"Extracellular vesicles in physiological and pathological conditions","volume":"27","author":"Yuana","year":"2013","journal-title":"Blood Rev."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Eldh, M., Ekstr\u00f6m, K., Valadi, H., Sj\u00f6strand, M., Olsson, B., Jern\u00e5s, M., and L\u00f6tvall, J. (2010). Exosomes Communicate Protective Messages during Oxidative Stress; Possible Role of Exosomal Shuttle RNA. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0015353"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1172\/JCI76693","article-title":"Annexin A1\u2013containing extracellular vesicles and polymeric nanoparticles promote epithelial wound repair","volume":"125","author":"Leoni","year":"2015","journal-title":"J. Clin. Investig."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3862","DOI":"10.1182\/blood.V91.10.3862","article-title":"Biologically active Fas antigen and its cognate ligand are expressed on plasma membrane-derived extracellular vesicles","volume":"91","author":"Albanese","year":"1998","journal-title":"Blood"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"275","DOI":"10.3389\/fphys.2017.00275","article-title":"Endothelial Extracellular Vesicles-Promises and Challenges","volume":"8","author":"Hromada","year":"2017","journal-title":"Front. Physiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2723","DOI":"10.3389\/fimmu.2018.02723","article-title":"Large Extracellular Vesicles: Have We Found the Holy Grail of Inflammation?","volume":"9","author":"Urban","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Berezin, A.E., and Berezin, A.A. (2020). Endothelial cell-derived extracellular vesicles in atherosclerosis: The emerging value for diagnosis, risk stratification and prognostication. Vessel Plus, 4.","DOI":"10.20517\/2574-1209.2020.03"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"828","DOI":"10.7150\/ijbs.19776","article-title":"Platelet-derived Extracellular Vesicles: An Emerging Therapeutic Approach","volume":"13","author":"Tao","year":"2017","journal-title":"Int. J. Biol. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Gasecka, A., Nieuwland, R., and Siljander, P.R.-M. (2019). Platelet-Derived Extracellular Vesicles. Platelets, Academic Press.","DOI":"10.1016\/B978-0-12-813456-6.00022-9"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1161\/CIRCRESAHA.110.233403","article-title":"Leukocyte-derived microparticles in vascular homeostasis","volume":"110","year":"2012","journal-title":"Circ. Res."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Hong, C.-W. (2018). Extracellular Vesicles of Neutrophils. Immune Netw., 18.","DOI":"10.4110\/in.2018.18.e43"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.3389\/fimmu.2019.01037","article-title":"Role of Neutrophil Extracellular Traps and Vesicles in Regulating Vascular Endothelial Permeability","volume":"10","author":"Ma","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1479","DOI":"10.3389\/fphar.2019.01479","article-title":"The Contrasting Role of Extracellular Vesicles in Vascular Inflammation and Tissue Repair","volume":"10","author":"Oggero","year":"2019","journal-title":"Front. Pharmacol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2905","DOI":"10.1113\/JP271340","article-title":"Emerging roles for vascular smooth muscle cell exosomes in calcification and coagulation","volume":"594","author":"Kapustin","year":"2016","journal-title":"J. Physiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.1039\/c3mb70544g","article-title":"Characterization of secreted vesicles from vascular smooth muscle cells","volume":"10","author":"Comelli","year":"2014","journal-title":"Mol. Biosyst."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.coph.2017.08.008","article-title":"Bone-derived exosomes","volume":"34","author":"Liu","year":"2017","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"846","DOI":"10.3389\/fendo.2019.00846","article-title":"Bone-Derived Extracellular Vesicles: Novel Players of Interorgan Crosstalk","volume":"10","author":"Li","year":"2019","journal-title":"Front. Endocrinol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Tsiapalis, D., and O\u2019Driscoll, L. (2020). Mesenchymal Stem Cell Derived Extracellular Vesicles for Tissue Engineering and Regenerative Medicine Applications. Cells, 9.","DOI":"10.3390\/cells9040991"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"C303","DOI":"10.1152\/ajpcell.00129.2019","article-title":"Role of extracellular vesicles in stem cell biology","volume":"317","author":"Bruno","year":"2019","journal-title":"Am. J. Physiol.-Cell Physiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1535750","DOI":"10.1080\/20013078.2018.1535750","article-title":"Minimal information for studies of extracellular vesicles 2018 (MISEV2018): A position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines","volume":"7","author":"Witwer","year":"2018","journal-title":"J. Extracell. Vesicles"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1016\/j.tibtech.2020.05.012","article-title":"Technologies and Standardization in Research on Extracellular Vesicles","volume":"38","author":"Gandham","year":"2020","journal-title":"Trends Biotechnol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1016\/j.jmb.2015.09.019","article-title":"ExoCarta: A Web-Based Compendium of Exosomal Cargo","volume":"428","author":"Keerthikumar","year":"2016","journal-title":"J. Mol. Biol."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Kim, D.-K., Kang, B., Kim, O.Y., Choi, D., Lee, J., Kim, S.R., Go, G., Yoon, Y.J., Kim, J.H., and Jang, S.C. (2013). EVpedia: An integrated database of high-throughput data for systemic analyses of extracellular vesicles. J. Extracell. Vesicles, 2.","DOI":"10.3402\/jev.v2i0.20384"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"D516","DOI":"10.1093\/nar\/gky1029","article-title":"Vesiclepedia 2019: A compendium of RNA, proteins, lipids and metabolites in extracellular vesicles","volume":"47","author":"Pathan","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"F1430","DOI":"10.1152\/ajprenal.00318.2018","article-title":"Vesicles bearing gifts: The functional importance of micro-RNA transfer in extracellular vesicles in chronic kidney disease","volume":"315","author":"Abbasian","year":"2018","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Zietzer, A., Steffen, E., Niepmann, S., D\u00fcsing, P., Hosen, M.R., Liu, W., Jamme, P., Al-Kassou, B., Goody, P.R., and Zimmer, S. (2020). MicroRNA-mediated vascular intercellular communication is altered in chronic kidney disease. Cardiovasc. Res.","DOI":"10.1093\/cvr\/cvaa322"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2511","DOI":"10.1093\/ndt\/gfp066","article-title":"The relationship between circulating endothelial microparticles and arterial stiffness and atherosclerosis in children with chronic kidney disease","volume":"24","author":"Dursun","year":"2009","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1873","DOI":"10.1093\/ndt\/gfr573","article-title":"Predictive value of circulating endothelial microparticles for cardiovascular mortality in end-stage renal failure: A pilot study","volume":"27","author":"Amabile","year":"2012","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"227","DOI":"10.2215\/CJN.03260509","article-title":"Effect of different dialysis modalities on microinflammatory status and endothelial damage","volume":"5","author":"Merino","year":"2010","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"3381","DOI":"10.1681\/ASN.2005050535","article-title":"Circulating Endothelial Microparticles Are Associated with Vascular Dysfunction in Patients with End-Stage Renal Failure","volume":"16","author":"Amabile","year":"2005","journal-title":"JASN"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1111\/j.1538-7836.2005.01780.x","article-title":"Elevation of circulating endothelial microparticles in patients with chronic renal failure","volume":"4","author":"Faure","year":"2006","journal-title":"J. Thromb. Haemost."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1446","DOI":"10.1093\/ndt\/gfr474","article-title":"Chronic renal failure is accompanied by endothelial activation and a large increase in microparticle numbers with reduced procoagulant capacity","volume":"27","author":"Trappenburg","year":"2012","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Hsu, C.-Y., Huang, P.-H., Chiang, C.-H., Leu, H.-B., Huang, C.-C., Chen, J.-W., and Lin, S.-J. (2013). Increased circulating endothelial apoptotic microparticle to endothelial progenitor cell ratio is associated with subsequent decline in glomerular filtration rate in hypertensive patients. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0068644"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1161\/01.HYP.0000259667.22309.df","article-title":"In vivo shear stress determines circulating levels of endothelial microparticles in end-stage renal disease","volume":"49","author":"Boulanger","year":"2007","journal-title":"Hypertension"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1093\/ndt\/gfv337","article-title":"Effects of lipid-lowering treatment on circulating microparticles in patients with diabetes mellitus and chronic kidney disease","volume":"31","author":"Almquist","year":"2016","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1757","DOI":"10.1046\/j.1523-1755.2002.00627.x","article-title":"Circulating platelet-derived microparticles with procoagulant activity may be a potential cause of thrombosis in uremic patients","volume":"62","author":"Ando","year":"2002","journal-title":"Kidney Int."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Burton, J.O., Hamali, H.A., Singh, R., Abbasian, N., Parsons, R., Patel, A.K., Goodall, A.H., and Brunskill, N.J. (2013). Elevated levels of procoagulant plasma microvesicles in dialysis patients. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0072663"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2667","DOI":"10.1182\/blood-2016-10-744060","article-title":"Indoxyl sulfate induces platelet hyperactivity and contributes to chronic kidney disease-associated thrombosis in mice","volume":"129","author":"Yang","year":"2017","journal-title":"Blood"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"F673","DOI":"10.1152\/ajprenal.00013.2016","article-title":"Markers of endothelial damage in patients with chronic kidney disease on hemodialysis","volume":"312","author":"Carmona","year":"2017","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"247","DOI":"10.5551\/jat.26658","article-title":"Levels of circulating microparticles in patients with chronic cardiorenal disease","volume":"22","author":"Chen","year":"2015","journal-title":"J. Atheroscler. Thromb."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Benito-Martin, A., Ucero, A.C., Zubiri, I., Posada-Ayala, M., Fernandez-Fernandez, B., Cannata-Ortiz, P., Sanchez-Nino, M.D., Ruiz-Ortega, M., Egido, J., and Alvarez-Llamas, G. (2013). Osteoprotegerin in exosome-like vesicles from human cultured tubular cells and urine. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0072387"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.cca.2013.10.003","article-title":"CD2AP mRNA in urinary exosome as biomarker of kidney disease","volume":"428","author":"Lv","year":"2014","journal-title":"Clin. Chim. Acta"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1416","DOI":"10.1038\/sj.ki.5000306","article-title":"Increase of circulating neutrophil and platelet microparticles during acute vasculitis and hemodialysis","volume":"69","author":"Daniel","year":"2006","journal-title":"Kidney Int."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"3794","DOI":"10.1093\/ndt\/gfr485","article-title":"Circulating microRNA expression is reduced in chronic kidney disease","volume":"26","author":"Neal","year":"2011","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"118295","DOI":"10.1016\/j.lfs.2020.118295","article-title":"Advanced chronic kidney disease is associated with higher serum concentration of monocyte microparticles","volume":"260","author":"Fonseca","year":"2020","journal-title":"Life Sci."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.trim.2014.06.006","article-title":"Early posttransplant changes in circulating endothelial microparticles in patients with kidney transplantation","volume":"31","author":"Qamri","year":"2014","journal-title":"Transpl. Immunol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2360","DOI":"10.1111\/j.1600-6143.2008.02399.x","article-title":"Impact of immunosuppressive treatment on endothelial biomarkers after kidney transplantation","volume":"8","author":"Paul","year":"2008","journal-title":"Am. J. Transplant."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"e007818","DOI":"10.1161\/JAHA.117.007818","article-title":"Endothelial Microparticles and Systemic Complement Activation in Patients With Chronic Kidney Disease","volume":"7","author":"Jalal","year":"2018","journal-title":"J. Am. Heart Assoc."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1681\/ASN.2017050523","article-title":"Exosomal CCL2 from Tubular Epithelial Cells Is Critical for Albumin-Induced Tubulointerstitial Inflammation","volume":"29","author":"Lv","year":"2018","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_81","first-page":"456","article-title":"Acute effects of haemodialysis on circulating microparticles","volume":"12","author":"Mobarrez","year":"2018","journal-title":"Clin. Kidney J."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1139\/cjpp-2017-0285","article-title":"Short-term effects of hemodiafiltration versus conventional hemodialysis on erythrocyte performance","volume":"96","author":"Georgatzakou","year":"2018","journal-title":"Can. J. Physiol. Pharmacol."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Ruzicka, M., Xiao, F., Abujrad, H., Al-Rewashdy, Y., Tang, V.A., Langlois, M.-A., Sorisky, A., Ooi, T.C., and Burger, D. (2019). Effect of hemodialysis on extracellular vesicles and circulating submicron particles. BMC Nephrol., 20.","DOI":"10.1186\/s12882-019-1459-y"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1681\/ASN.2011121140","article-title":"Effect of online hemodiafiltration on all-cause mortality and cardiovascular outcomes","volume":"23","author":"Grooteman","year":"2012","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1038\/ki.2014.9","article-title":"Online hemodiafiltration reduces systemic inflammation compared to low-flux hemodialysis","volume":"86","author":"Bots","year":"2014","journal-title":"Kidney Int."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"2372","DOI":"10.4049\/jimmunol.1800747","article-title":"Online Hemodiafiltration Inhibits Inflammation-Related Endothelial Dysfunction and Vascular Calcification of Uremic Patients Modulating miR-223 Expression in Plasma Extracellular Vesicles","volume":"202","author":"Cavallari","year":"2019","journal-title":"J. Immunol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.1681\/ASN.2011121175","article-title":"Normal and pathologic concentrations of uremic toxins","volume":"23","author":"Duranton","year":"2012","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1111\/j.1525-139X.2009.00574.x","article-title":"The role of EUTox in uremic toxin research","volume":"22","author":"Vanholder","year":"2009","journal-title":"Semin. Dial."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Favretto, G., da Cunha, R.S., Dalboni, M.A., de Oliveira, R.B., de Carvalho Barreto, F., Massy, Z.A., and Stinghen, A.E.M. (2019). Endothelial Microparticles in Uremia: Biomarkers and Potential Therapeutic Targets. Toxins, 11.","DOI":"10.3390\/toxins11050267"},{"key":"ref_90","first-page":"485","article-title":"Significance of Platelet-Derived Microparticles in Uremia","volume":"63","author":"Nomura","year":"1993","journal-title":"NEF"},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Gao, C., Xie, R., Yu, C., Ma, R., Dong, W., Meng, H., Zhang, Y., Si, Y., Zhang, Z., and Novakovic, V. (2015). Thrombotic Role of Blood and Endothelial Cells in Uremia through Phosphatidylserine Exposure and Microparticle Release. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0142835"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1053\/j.ajkd.2009.04.022","article-title":"The uremic retention solute p-cresyl sulfate and markers of endothelial damage","volume":"54","author":"Meijers","year":"2009","journal-title":"Am. J. Kidney Dis."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.bbrc.2009.06.095","article-title":"Heat shock protein 70 is secreted from endothelial cells by a non-classical pathway involving exosomes","volume":"387","author":"Zhan","year":"2009","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1159\/000326297","article-title":"Clopidogrel effectively suppresses endothelial microparticle generation induced by indoxyl sulfate via inhibition of the p38 mitogen-activated protein kinase pathway","volume":"32","author":"Ryu","year":"2011","journal-title":"Blood Purif."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1007\/s00726-011-1196-4","article-title":"Homocysteine enhances clot-promoting activity of endothelial cells via phosphatidylserine externalization and microparticles formation","volume":"43","author":"Zhu","year":"2012","journal-title":"Amino Acids"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1997","DOI":"10.1007\/s00726-014-1755-6","article-title":"Homocysteine induces procoagulant activity of red blood cells via phosphatidylserine exposure and microparticles generation","volume":"46","author":"Xie","year":"2014","journal-title":"Amino Acids"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"4390","DOI":"10.3390\/toxins7114390","article-title":"Indolic uremic solutes enhance procoagulant activity of red blood cells through phosphatidylserine exposure and microparticle release","volume":"7","author":"Gao","year":"2015","journal-title":"Toxins"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"666","DOI":"10.3389\/fphys.2017.00666","article-title":"Microvesicles Derived from Indoxyl Sulfate Treated Endothelial Cells Induce Endothelial Progenitor Cells Dysfunction","volume":"8","author":"Carmona","year":"2017","journal-title":"Front. Physiol."},{"key":"ref_99","first-page":"69","article-title":"Endothelial microparticle formation in moderate concentrations of homocysteine and methionine in vitro","volume":"16","author":"Janawa","year":"2011","journal-title":"Cell. Mol. Biol. Lett."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1016\/j.csbj.2020.04.006","article-title":"Microvesicles from indoxyl sulfate-treated endothelial cells induce vascular calcification in vitro","volume":"18","author":"Alique","year":"2020","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"11","DOI":"10.4174\/astr.2017.93.1.11","article-title":"The effects of indoxyl sulfate-induced endothelial microparticles on neointimal hyperplasia formation in an ex vivo model","volume":"93","author":"Ryu","year":"2017","journal-title":"Ann. Surg. Treat. Res."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1159\/000496796","article-title":"Indoxyl Sulfate-Induced Extracellular Vesicles Released from Endothelial Cells Stimulate Vascular Smooth Muscle Cell Proliferation by Inducing Transforming Growth Factor-Beta Production","volume":"56","author":"Ryu","year":"2019","journal-title":"J. Vasc. Res."},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Addi, T., Dou, L., and Burtey, S. (2018). Tryptophan-Derived Uremic Toxins and Thrombosis in Chronic Kidney Disease. Toxins, 10.","DOI":"10.3390\/toxins10100412"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"2152","DOI":"10.1681\/ASN.2014070642","article-title":"Hyperphosphatemia, Phosphoprotein Phosphatases, and Microparticle Release in Vascular Endothelial Cells","volume":"26","author":"Abbasian","year":"2015","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1038\/ki.2012.300","article-title":"High phosphate directly affects endothelial function by downregulating annexin II","volume":"83","author":"Stock","year":"2013","journal-title":"Kidney Int."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"3251","DOI":"10.1681\/ASN.2016111215","article-title":"MicroRNA-92a Mediates Endothelial Dysfunction in CKD","volume":"28","author":"Shang","year":"2017","journal-title":"JASN"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1038\/ncb2441","article-title":"Atheroprotective communication between endothelial cells and smooth muscle cells through miRNAs","volume":"14","author":"Hergenreider","year":"2012","journal-title":"Nat. Cell Biol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1161\/CIRCRESAHA.113.301792","article-title":"A role for the endothelium in vascular calcification","volume":"113","author":"Yao","year":"2013","journal-title":"Circ. Res."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/S0065-2423(04)39005-0","article-title":"Endothelial microparticles (EMP) as vascular disease markers","volume":"39","author":"Jimenez","year":"2005","journal-title":"Adv. Clin. Chem."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1038\/sj.ki.5002250","article-title":"Microinflammation induces endothelial damage in hemodialysis patients: The role of convective transport","volume":"72","author":"Ramirez","year":"2007","journal-title":"Kidney Int."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"8505","DOI":"10.1038\/srep08505","article-title":"Inflammation-induced endothelial cell-derived extracellular vesicles modulate the cellular status of pericytes","volume":"5","author":"Yamamoto","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"2804","DOI":"10.1002\/jcp.25985","article-title":"Roles of platelet-derived growth factor in vascular calcification","volume":"233","author":"Ouyang","year":"2018","journal-title":"J. Cell. Physiol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1253\/circj.CJ-11-0395","article-title":"Cardiovascular calcification: An inflammatory disease","volume":"75","author":"New","year":"2011","journal-title":"Circ. J."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"3183794","DOI":"10.1155\/2018\/3183794","article-title":"Young and Especially Senescent Endothelial Microvesicles Produce NADPH: The Fuel for Their Antioxidant Machinery","volume":"2018","author":"Bodega","year":"2018","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"78","DOI":"10.3389\/fcvm.2017.00078","article-title":"Extracellular Vesicles as Mediators of Cardiovascular Calcification","volume":"4","author":"Hutcheson","year":"2017","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.cca.2019.09.002","article-title":"Extracellular vesicles in vascular calcification","volume":"499","author":"Yang","year":"2019","journal-title":"Clin. Chim. Acta"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"2881","DOI":"10.1113\/JP271336","article-title":"Extracellular vesicles in cardiovascular disease: Are they Jedi or Sith?","volume":"594","author":"Osteikoetxea","year":"2016","journal-title":"J. Physiol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"F1302","DOI":"10.1152\/ajprenal.00114.2014","article-title":"Endothelial damage and vascular calcification in patients with chronic kidney disease","volume":"307","author":"Soriano","year":"2014","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1172\/JCI80851","article-title":"Sortilin mediates vascular calcification via its recruitment into extracellular vesicles","volume":"126","author":"Goettsch","year":"2016","journal-title":"J. Clin. Investig."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1161\/ATVBAHA.117.310578","article-title":"Chronic Kidney Disease Circulating Calciprotein Particles and Extracellular Vesicles Promote Vascular Calcification: A Role for GRP (Gla-Rich Protein)","volume":"38","author":"Viegas","year":"2018","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"eabb1244","DOI":"10.1126\/sciadv.abb1244","article-title":"Annexin A1\u2013dependent tethering promotes extracellular vesicle aggregation revealed with single\u2013extracellular vesicle analysis","volume":"6","author":"Rogers","year":"2020","journal-title":"Sci. Adv."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1161\/CIRCRESAHA.119.316159","article-title":"Reactive Oxygen-Forming Nox5 Links Vascular Smooth Muscle Cell Phenotypic Switching and Extracellular Vesicle-Mediated Vascular Calcification","volume":"127","author":"Furmanik","year":"2020","journal-title":"Circ. Res."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1096\/fj.14-249706","article-title":"Endothelial microparticles mediate inflammation-induced vascular calcification","volume":"29","author":"Merino","year":"2015","journal-title":"FASEB J."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"778","DOI":"10.18632\/aging.101191","article-title":"Microvesicles from the plasma of elderly subjects and from senescent endothelial cells promote vascular calcification","volume":"9","author":"Alique","year":"2017","journal-title":"Aging"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.yjmcc.2013.12.009","article-title":"Mechanical strain induces the production of spheroid mineralized microparticles in the aortic valve through a RhoA\/ROCK-dependent mechanism","volume":"67","author":"Bouchareb","year":"2014","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/j.kint.2017.07.019","article-title":"Matrix vesicles induce calcification of recipient vascular smooth muscle cells through multiple signaling pathways","volume":"93","author":"Chen","year":"2018","journal-title":"Kidney Int."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1161\/CIRCRESAHA.110.238808","article-title":"Calcium Regulates Key Components of Vascular Smooth Muscle Cell\u2013Derived Matrix Vesicles to Enhance Mineralization","volume":"109","author":"Kapustin","year":"2011","journal-title":"Circ. Res."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1161\/ATVBAHA.117.309513","article-title":"Oligogalacturonic Acid Inhibits Vascular Calcification by Two Mechanisms: Inhibition of Vascular Smooth Muscle Cell Osteogenic Conversion and Interaction With Collagen","volume":"37","author":"Hodroge","year":"2017","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"589761","DOI":"10.3389\/fcell.2020.589761","article-title":"GFOGER Peptide Modifies the Protein Content of Extracellular Vesicles and Inhibits Vascular Calcification","volume":"8","author":"Mansour","year":"2020","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"2985","DOI":"10.1002\/jcp.25935","article-title":"End stage renal disease-induced hypercalcemia may promote aortic valve calcification via Annexin VI enrichment of valve interstitial cell derived-matrix vesicles","volume":"232","author":"Cui","year":"2017","journal-title":"J. Cell. Physiol."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1161\/CIRCRESAHA.113.301036","article-title":"Macrophage-derived matrix vesicles: An alternative novel mechanism for microcalcification in atherosclerotic plaques","volume":"113","author":"New","year":"2013","journal-title":"Circ. Res."},{"key":"ref_132","doi-asserted-by":"crossref","unstructured":"Chen, Q., Bei, J.-J., Liu, C., Feng, S.-B., Zhao, W.-B., Zhou, Z., Yu, Z.-P., Du, X.-J., and Hu, H.-Y. (2016). HMGB1 Induces Secretion of Matrix Vesicles by Macrophages to Enhance Ectopic Mineralization. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0156686"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"36","DOI":"10.3389\/fcvm.2018.00036","article-title":"Initiation and Propagation of Vascular Calcification Is Regulated by a Concert of Platelet- and Smooth Muscle Cell-Derived Extracellular Vesicles","volume":"5","author":"Schurgers","year":"2018","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"2895","DOI":"10.1113\/JP271338","article-title":"Extracellular vesicles in cardiovascular calcification: Expanding current paradigms","volume":"594","author":"Krohn","year":"2016","journal-title":"J. Physiol."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1016\/j.kint.2017.08.036","article-title":"Not all vascular smooth muscle cell exosomes calcify equally in chronic kidney disease","volume":"93","author":"Dusso","year":"2018","journal-title":"Kidney Int."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1016\/S0021-9258(17)35301-2","article-title":"Collagen-binding proteins in collagenase-released matrix vesicles from cartilage. Interaction between matrix vesicle proteins and different types of collagen","volume":"266","author":"Wu","year":"1991","journal-title":"J. Biol. Chem."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1074\/jbc.275.1.35","article-title":"The collagen-binding A-domains of integrins alpha(1)beta(1) and alpha(2)beta(1) recognize the same specific amino acid sequence, GFOGER, in native (triple-helical) collagens","volume":"275","author":"Knight","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"187","DOI":"10.3389\/fcvm.2018.00187","article-title":"Roles and Regulation of Extracellular Vesicles in Cardiovascular Mineral Metabolism","volume":"5","author":"Blaser","year":"2018","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"661","DOI":"10.3389\/fphar.2020.00661","article-title":"Role of Macrophages in the Progression and Regression of Vascular Calcification","volume":"11","author":"Li","year":"2020","journal-title":"Front. Pharmacol."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1161\/ATVBAHA.117.309795","article-title":"Extracellular Vesicles Secreted by Atherogenic Macrophages Transfer MicroRNA to Inhibit Cell Migration","volume":"38","author":"Nguyen","year":"2018","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"F375","DOI":"10.1152\/ajprenal.00266.2016","article-title":"A perspective on chronic kidney disease progression","volume":"312","author":"Zhong","year":"2017","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"13368","DOI":"10.1073\/pnas.0403453101","article-title":"Identification and proteomic profiling of exosomes in human urine","volume":"101","author":"Pisitkun","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/nep.12005","article-title":"Exosomes and the kidney: Blaming the messenger","volume":"18","author":"Fang","year":"2013","journal-title":"Nephrology"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"267","DOI":"10.5500\/wjt.v5.i4.267","article-title":"Dynamics of circulating microparticles in chronic kidney disease and transplantation: Is it really reliable marker?","volume":"5","author":"Dursun","year":"2015","journal-title":"World J. Transplant."},{"key":"ref_145","first-page":"6","article-title":"Urinary extracellular vesicles as source of biomarkers in kidney diseases","volume":"6","author":"Bancu","year":"2015","journal-title":"Front. Immunol."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"657086","DOI":"10.1155\/2015\/657086","article-title":"Exosomes: Novel biomarkers for clinical diagnosis","volume":"2015","author":"Lin","year":"2015","journal-title":"Sci. World J."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"F844","DOI":"10.1152\/ajprenal.00429.2016","article-title":"Extracellular vesicles in diagnosis and therapy of kidney diseases","volume":"311","author":"Zhang","year":"2016","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"2251","DOI":"10.4103\/0366-6999.213965","article-title":"Urinary Biomarkers for Chronic Kidney Disease with a Focus on Gene Transcript","volume":"130","author":"Lyu","year":"2017","journal-title":"Chin. Med. J."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1007\/s00441-017-2621-0","article-title":"Urinary extracellular vesicles. A promising shortcut to novel biomarker discoveries","volume":"369","author":"Barreiro","year":"2017","journal-title":"Cell Tissue Res."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1042\/BST20120090","article-title":"Analysis of urinary microRNAs in chronic kidney disease","volume":"40","author":"Beltrami","year":"2012","journal-title":"Biochem. Soc. Trans."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1161\/CIRCRESAHA.113.300937","article-title":"MicroRNA in cardiovascular calcification: Focus on targets and extracellular vesicle delivery mechanisms","volume":"112","author":"Goettsch","year":"2013","journal-title":"Circ. Res."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.7150\/ijbs.6100","article-title":"Isolation and quantification of microRNAs from urinary exosomes\/microvesicles for biomarker discovery","volume":"9","author":"Lv","year":"2013","journal-title":"Int. J. Biol. Sci."},{"key":"ref_153","doi-asserted-by":"crossref","unstructured":"Cheng, L., Sharples, R.A., Scicluna, B.J., and Hill, A.F. (2014). Exosomes provide a protective and enriched source of miRNA for biomarker profiling compared to intracellular and cell-free blood. J. Extracell. Vesicles, 3.","DOI":"10.3402\/jev.v3.23743"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"393109","DOI":"10.1155\/2014\/393109","article-title":"Stability of miR-126 in Urine and Its Potential as a Biomarker for Renal Endothelial Injury with Diabetic Nephropathy","volume":"2014","author":"Liu","year":"2014","journal-title":"Int. J. Endocrinol."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1586\/14737159.2015.1009449","article-title":"miRNAs in urine: A mirror image of kidney disease?","volume":"15","author":"Papadopoulos","year":"2015","journal-title":"Expert Rev. Mol. Diagn."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1111\/eci.12420","article-title":"Circulating and urinary microRNA profile in focal segmental glomerulosclerosis: A pilot study","volume":"45","author":"Ramezani","year":"2015","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"2631","DOI":"10.1681\/ASN.2016111213","article-title":"MicroRNA-23a and MicroRNA-27a Mimic Exercise by Ameliorating CKD-Induced Muscle Atrophy","volume":"28","author":"Wang","year":"2017","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_158","doi-asserted-by":"crossref","unstructured":"Mohan, A., Singh, R.S., Kumari, M., Garg, D., Upadhyay, A., Ecelbarger, C.M., Tripathy, S., and Tiwari, S. (2016). Urinary Exosomal microRNA-451-5p Is a Potential Early Biomarker of Diabetic Nephropathy in Rats. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0154055"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"F1220","DOI":"10.1152\/ajprenal.00148.2013","article-title":"MicroRNA-29c in urinary exosome\/microvesicle as a biomarker of renal fibrosis","volume":"305","author":"Lv","year":"2013","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"ref_160","doi-asserted-by":"crossref","unstructured":"Catalano, M., and O\u2019Driscoll, L. (2019). Inhibiting extracellular vesicles formation and release: A review of EV inhibitors. J. Extracell. Vesicles, 9.","DOI":"10.1080\/20013078.2019.1703244"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"30087","DOI":"10.3402\/jev.v4.30087","article-title":"Applying extracellular vesicles based therapeutics in clinical trials - an ISEV position paper","volume":"4","author":"Lener","year":"2015","journal-title":"J. Extracell. Vesicles"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"8161","DOI":"10.1038\/s41598-018-26411-7","article-title":"High-throughput screening identified selective inhibitors of exosome biogenesis and secretion: A drug repurposing strategy for advanced cancer","volume":"8","author":"Datta","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/0049-3848(93)90163-I","article-title":"The effects of calpeptin (a calpain specific inhibitor) on agonist induced microparticle formation from the platelet plasma membrane","volume":"71","author":"Yano","year":"1993","journal-title":"Thromb. Res."},{"key":"ref_164","doi-asserted-by":"crossref","unstructured":"Yun, C.W., and Lee, S.H. (2019). Potential and Therapeutic Efficacy of Cell-based Therapy Using Mesenchymal Stem Cells for Acute\/chronic Kidney Disease. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20071619"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/s40824-016-0068-0","article-title":"Umbilical cord mesenchymal stem cells derived extracellular vesicles can safely ameliorate the progression of chronic kidney diseases","volume":"20","author":"Nassar","year":"2016","journal-title":"Biomater. Res."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"1474","DOI":"10.1093\/ndt\/gfr015","article-title":"Microvesicles derived from human adult mesenchymal stem cells protect against ischaemia-reperfusion-induced acute and chronic kidney injury","volume":"26","author":"Gatti","year":"2011","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1111\/j.1440-1797.2012.01589.x","article-title":"Bone marrow stem cells-derived microvesicles protect against renal injury in the mouse remnant kidney model","volume":"17","author":"He","year":"2012","journal-title":"Nephrology"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/s13287-015-0012-6","article-title":"Mesenchymal stem cell-derived microparticles ameliorate peritubular capillary rarefaction via inhibition of endothelial-mesenchymal transition and decrease tubulointerstitial fibrosis in unilateral ureteral obstruction","volume":"6","author":"Choi","year":"2015","journal-title":"Stem. Cell Res. Ther."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1111\/nep.12490","article-title":"Micro-vesicles derived from bone marrow stem cells protect the kidney both in vivo and in vitro by microRNA-dependent repairing","volume":"20","author":"He","year":"2015","journal-title":"Nephrology"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.1038\/mt.2016.90","article-title":"Mesenchymal Stem Cells Deliver Exogenous MicroRNA-let7c via Exosomes to Attenuate Renal Fibrosis","volume":"24","author":"Wang","year":"2016","journal-title":"Mol. Ther."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.kint.2016.12.023","article-title":"Mesenchymal stem cell-derived extracellular vesicles attenuate kidney inflammation","volume":"92","author":"Eirin","year":"2017","journal-title":"Kidney Int."},{"key":"ref_172","doi-asserted-by":"crossref","unstructured":"van Koppen, A., Joles, J.A., van Balkom, B.W.M., Lim, S.K., de Kleijn, D., Giles, R.H., and Verhaar, M.C. (2012). Human embryonic mesenchymal stem cell-derived conditioned medium rescues kidney function in rats with established chronic kidney disease. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0038746"},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1111\/j.1523-1755.2004.00784.x","article-title":"Uremia causes endothelial progenitor cell deficiency","volume":"66","author":"Bahlmann","year":"2004","journal-title":"Kidney Int."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1161\/01.ATV.0000133488.56221.4a","article-title":"Decreased number and impaired angiogenic function of endothelial progenitor cells in patients with chronic renal failure","volume":"24","author":"Choi","year":"2004","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"21","DOI":"10.5414\/CN107318","article-title":"Decrease in endothelial progenitor cells associated with inflammation, but not with endothelial dysfunction in chronic hemodialysis patients","volume":"79","author":"Ozkok","year":"2013","journal-title":"Clin Nephrol"},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"2265","DOI":"10.1093\/ndt\/gfm943","article-title":"Association between endothelial progenitor cell depletion in blood and mild-to-moderate renal insufficiency in stable angina","volume":"23","author":"Surdacki","year":"2008","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.1038\/ki.2008.495","article-title":"Low circulating CD34+ cell count is associated with poor prognosis in chronic hemodialysis patients","volume":"74","author":"Maruyama","year":"2008","journal-title":"Kidney Int."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1681\/ASN.2009111119","article-title":"Dysfunctional endothelial progenitor cells in chronic kidney disease","volume":"21","author":"Goligorsky","year":"2010","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1016\/S0272-6386(04)01083-2","article-title":"Increased total number but impaired migratory activity and adhesion of endothelial progenitor cells in patients on long-term hemodialysis","volume":"44","author":"Herbrig","year":"2004","journal-title":"Am. J. Kidney Dis."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1159\/000452604","article-title":"Indoxyl Sulfate Impairs Endothelial Progenitor Cells and Might Contribute to Vascular Dysfunction in Patients with Chronic Kidney Disease","volume":"41","author":"Lin","year":"2016","journal-title":"Kidney Blood Press Res."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"F325","DOI":"10.1152\/ajprenal.00019.2010","article-title":"Bone marrow-derived endothelial progenitor cells confer renal protection in a murine chronic renal failure model","volume":"299","author":"Sangidorj","year":"2010","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"2440","DOI":"10.1182\/blood-2007-03-078709","article-title":"Endothelial progenitor cell\u2013derived microvesicles activate an angiogenic program in endothelial cells by a horizontal transfer of mRNA","volume":"110","author":"Deregibus","year":"2007","journal-title":"Blood"},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1093\/ndt\/gfu364","article-title":"Endothelial progenitor cell-derived extracellular vesicles protect from complement-mediated mesangial injury in experimental anti-Thy1.1 glomerulonephritis","volume":"30","author":"Cantaluppi","year":"2015","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1038\/ki.2012.105","article-title":"Microvesicles derived from endothelial progenitor cells protect the kidney from ischemia\u2013reperfusion injury by microRNA-dependent reprogramming of resident renal cells","volume":"82","author":"Cantaluppi","year":"2012","journal-title":"Kidney Int."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"e130","DOI":"10.1093\/nar\/gks463","article-title":"Plasma exosomes can deliver exogenous short interfering RNA to monocytes and lymphocytes","volume":"40","author":"Wahlgren","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1038\/nbt.1807","article-title":"Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes","volume":"29","author":"Seow","year":"2011","journal-title":"Nat. Biotechnol."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1038\/mt.2012.180","article-title":"Systemically injected exosomes targeted to EGFR deliver antitumor microRNA to breast cancer cells","volume":"21","author":"Ohno","year":"2013","journal-title":"Mol. Ther."}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/12\/12\/811\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:47:54Z","timestamp":1760179674000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/12\/12\/811"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,21]]},"references-count":187,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["toxins12120811"],"URL":"https:\/\/doi.org\/10.3390\/toxins12120811","relation":{},"ISSN":["2072-6651"],"issn-type":[{"value":"2072-6651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,21]]}}}