{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T23:32:41Z","timestamp":1784763161061,"version":"3.55.0"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,5,8]],"date-time":"2023-05-08T00:00:00Z","timestamp":1683504000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Urinary extracellular vesicles (uEVs) can be released by different cell types facing the urogenital tract and are involved in cellular trafficking, differentiation and survival. UEVs can be easily detected in urine and provide pathophysiological information \u201c<jats:italic>in vivo<\/jats:italic>\u201d without the need of a biopsy. Based on these premises, we hypothesized that uEVs proteomic profile may serve as a valuable tool in the differential characterization between Essential Hypertension (EH) and primary aldosteronism (PA).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients with essential hypertension (EH) and PA were enrolled in the study (EH= 12, PA=24: 11 Bilateral Primary Aldosteronism subtype (BPA) and 13 Aldosterone Producing Adenoma (APA)). Clinical and biochemical parameters were available for all the subjects. UEVs were isolated from urine by ultracentrifugation and analysed by Transmission Electron Microscopy (TEM) and nanotrack particle analysis (NTA). UEVs protein content was investigated through an untargeted MS-based approach. Statistical and network analysis was performed to identify potential candidates for the identification and classification of PA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>MS analysis provided more than 300 protein identifications. Exosomal markers CD9 and CD63 were detected in all samples. Several molecules characterizing EH <jats:italic>vs<\/jats:italic> PA patients as well as BPA and APA subtypes were identified after statistical elaboration and filtering of the results. In particular, some key proteins involved in water reabsorption mechanisms, such as AQP1 and AQP2, were among the best candidates for discriminating EH <jats:italic>vs<\/jats:italic> PA, as well as A1AG1 (AGP1).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Through this proteomic approach, we identified uEVs molecular indicators that can improve PA characterization and help in the gain of insights of the pathophysiological features of this disease. In particular, PA was characterized by a reduction of AQP1 and AQP2 expression as compared with EH.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2023.1096441","type":"journal-article","created":{"date-parts":[[2023,5,8]],"date-time":"2023-05-08T04:50:53Z","timestamp":1683521453000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":14,"title":["Proteomic analysis of urinary extracellular vesicles highlights specific signatures for patients with primary aldosteronism"],"prefix":"10.3389","volume":"14","author":[{"given":"Lorenzo","family":"Bertolone","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annalisa","family":"Castagna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcello","family":"Manfredi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domenica","family":"De Santis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Ambrosani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Antinori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Mulatero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Danese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilio","family":"Marengo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elettra","family":"Barberis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariangela","family":"Veneri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Martinelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simonetta","family":"Friso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Pizzolo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliviero","family":"Olivieri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,5,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S0828-282X(08)70617-2","article-title":"World hypertension day and global awareness","volume":"24","author":"Chockalingam","year":"2008","journal-title":"Can J Cardiol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3803\/EnM.2019.34.4.355","article-title":"Molecular mechanisms of primary aldosteronism","volume":"34","author":"Tevosian","year":"2019","journal-title":"Endocrinol Metab"},{"key":"B3","doi-asserted-by":"publisher","first-page":"e12093","DOI":"10.1002\/jev2.12093","article-title":"Urinary extracellular vesicles: a position paper by the urine task force of the international society for extracellular vesicles","volume":"10","author":"Erdbrugger","year":"2021","journal-title":"J Extracell Vesicles"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2017.00037","article-title":"Extracellular vesicles in renal pathophysiology","volume":"4","author":"Pomatto","year":"2017","journal-title":"Front Mol Biosci"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1100\/tsw.2009.128","article-title":"Urinary exosomes","volume":"9","author":"Dimov","year":"2009","journal-title":"Thescientificworldjo"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfu362","article-title":"Urinary exosomes in the diagnosis of gitelman and bartter syndromes","volume":"30","author":"Corbetta","year":"2015","journal-title":"Nephrol Dial Transplant"},{"key":"B7","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1681\/ASN.2015010074","article-title":"Extracellular vesicles in renal diseases: more than novel biomarkers","volume":"27","author":"Erdbrugger","year":"2016","journal-title":"J Am Soc Nephrol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"e13020","DOI":"10.1111\/cmi.13020","article-title":"Urinary exosome as a potential biomarker for urinary tract infection","volume":"21","author":"Mizutani","year":"2019","journal-title":"Cell Microbiol"},{"key":"B9","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1681\/ASN.2015111221","article-title":"In primary aldosteronism, mineralocorticoids influence exosomal sodium-chloride cotransporter abundance","volume":"28","author":"Wolley","year":"2017","journal-title":"J Am Soc Nephrol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"741","DOI":"10.1161\/HYPERTENSIONAHA.112.198135","article-title":"The phosphorylated sodium chloride cotransporter in urinary exosomes is superior to prostasin as a marker for aldosteronism","volume":"60","author":"van der Lubbe","year":"2012","journal-title":"Hypertension"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2017.00230","article-title":"Urinary exosomes and their cargo: potential biomarkers for mineralocorticoid arterial hypertension","volume":"8","author":"Barros","year":"2017","journal-title":"Front Endocrinol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1210\/endocr\/bqab032","article-title":"Proteomic profile of urinary extracellular vesicles identifies AGP1 as a potential biomarker of primary aldosteronism","volume":"162","author":"Barros","year":"2021","journal-title":"Endocrinology"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2020081142","article-title":"Comparing approaches to normalize, quantify, and characterize urinary extracellular vesicles","volume":"32","author":"Blijdorp","year":"2021","journal-title":"J Am Soc Nephrol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.118.311342","article-title":"Omics of blood pressure and hypertension","volume":"122","author":"Arnett","year":"2018","journal-title":"Circ Res"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1080\/14789450.2019.1632197","article-title":"Proteomic investigations into hypertension: what's new and how might it affect clinical practice","volume":"16","author":"Corbacho-Alonso","year":"2019","journal-title":"Expert Rev Proteomics"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1039\/c3mb70538b","article-title":"Urinary protease inhibitor serpin B3 is higher in women and is further increased in female patients affected by aldosterone producing adenoma","volume":"10","author":"Olivieri","year":"2014","journal-title":"Mol Biosyst"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2006-0078","article-title":"Comparison of confirmatory tests for the diagnosis of primary aldosteronism","volume":"91","author":"Mulatero","year":"2006","journal-title":"J Clin Endocrinol Metab"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2003-032179","article-title":"Aldosterone to renin ratio in a primary care setting: the bussolengo study","volume":"89","author":"Olivieri","year":"2004","journal-title":"J Clin Endocrinol Metab"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.109.146613","article-title":"Impact of different diagnostic criteria during adrenal vein sampling on reproducibility of subtype diagnosis in patients with primary aldosteronism","volume":"55","author":"Mulatero","year":"2010","journal-title":"Hypertension"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1007\/978-94-017-9523-4_11","article-title":"Hormone-dependent changes in female urinary proteome","volume":"845","author":"Castagna","year":"2015","journal-title":"Adv Exp Med Biol"},{"key":"B21","doi-asserted-by":"publisher","first-page":"17319","DOI":"10.1038\/srep17319","article-title":"Isolation of exosomes by differential centrifugation: theoretical analysis of a commonly used protocol","volume":"5","author":"Livshits","year":"2015","journal-title":"Sci Rep"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2013.12.002","article-title":"Renal aquaporins and water balance disorders","volume":"1840","author":"Kortenoeven","year":"2014","journal-title":"Biochim Biophys Acta"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.90762.2008","article-title":"Angiotensin II and hypertonicity modulate proximal tubular aquaporin 1 expression","volume":"297","author":"Bouley","year":"2009","journal-title":"Am J Physiol Renal Physiol"},{"key":"B24","doi-asserted-by":"publisher","first-page":"149","DOI":"10.12688\/f1000research.16654.1","article-title":"Vasopressin\u2013aquaporin-2 pathway: recent advances in understanding water balance disorders","volume":"8","author":"Ranieri","year":"2019","journal-title":"F1000Research"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M212388200","article-title":"Dual influence of aldosterone on AQP2 expression in cultured renal collecting duct principal cells","volume":"278","author":"Hasler","year":"2003","journal-title":"J Biol Chem"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00431.2006","article-title":"Long-term aldosterone treatment induces decreased apical but increased basolateral expression of AQP2 in CCD of rat kidney","volume":"293","author":"de Seigneux","year":"2007","journal-title":"Am J Physiol Renal Physiol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1210\/JC.2015-2007","article-title":"Deciphering the role of vasopressin in primary aldosteronism","volume":"100","author":"Nogueira-Silva","year":"2015","journal-title":"J Clin Endocrinol Metab"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00242.2019","article-title":"In human nephrectomy specimens, the kidney level of tubular transport proteins does not correlate with their abundance in urinary extracellular vesicles","volume":"317","author":"Sabaratnam","year":"2019","journal-title":"Am J Physiol Renal Physiol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.3390\/ijms17060957","article-title":"Aquaporins in urinary extracellular vesicles (Exosomes)","volume":"17","author":"Oshikawa","year":"2016","journal-title":"Int J Mol Sci"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1007\/s10157-018-1538-6","article-title":"AQP2 in human urine is predominantly localized to exosomes with preserved water channel activities","volume":"22","author":"Miyazawa","year":"2018","journal-title":"Clin Exp Nephrol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00463.2015","article-title":"An immunoassay for urinary extracellular vesicles","volume":"310","author":"Salih","year":"2016","journal-title":"Am J Physiol Renal Physiol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.01163-08","article-title":"Deficiency of the tetraspanin CD63 associated with kidney pathology but normal lysosomal function","volume":"29","author":"Schroder","year":"2009","journal-title":"Mol Cell Biol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.768734","article-title":"Serum alpha-1-Acid glycoprotein-1 and urinary extracellular vesicle miR-21-5p as potential biomarkers of primary aldosteronism","volume":"12","author":"Carvajal","year":"2021","journal-title":"Front Immunol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.transproceed.2013.08.079","article-title":"Urinary exosomes as a source of kidney dysfunction biomarker in renal transplantation","volume":"45","author":"Alvarez","year":"2013","journal-title":"Transplant Proc"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1007\/s12020-022-03103-x","article-title":"Clinical, biochemical, and miRNA profile of subjects with positive screening of primary aldosteronism and nonclassic apparent mineralocorticoid excess","volume":"77","author":"Tapia-Castillo","year":"2022","journal-title":"Endocrine"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00464.2014","article-title":"Carbonic anhydrase II binds to and increases the activity of the epithelial sodium-proton exchanger, NHE3","volume":"309","author":"Krishnan","year":"2015","journal-title":"Am J Physiology-Renal Physiol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2017.01108","article-title":"Deficiency of carbonic anhydrase II results in a urinary concentrating defect","volume":"8","author":"Krishnan","year":"2018","journal-title":"Front Physiol"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2023.1096441\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,8]],"date-time":"2023-05-08T04:50:57Z","timestamp":1683521457000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2023.1096441\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,8]]},"references-count":37,"alternative-id":["10.3389\/fendo.2023.1096441"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2023.1096441","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,8]]},"article-number":"1096441"}}