{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T19:54:05Z","timestamp":1790538845257,"version":"4.1.0"},"reference-count":44,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2019,6,4]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Hypertension may be associated with renal cellular injury. Cells in distress release extracellular vesicles (\n              <jats:styled-content style=\"fixed-case\">EV<\/jats:styled-content>\n              s), and their numbers in urine may reflect renal injury. Cellular senescence, an irreversible growth arrest in response to a noxious milieu, is characterized by release of proinflammatory cytokines. We hypothesized that\n              <jats:styled-content style=\"fixed-case\">EV<\/jats:styled-content>\n              s released by senescent nephron cells can be identified in urine of patients with hypertension.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              We recruited patients with essential hypertension (\n              <jats:styled-content style=\"fixed-case\">EH<\/jats:styled-content>\n              ) or renovascular hypertension and healthy volunteers (n=14 each). Renal oxygenation was assessed using magnetic resonance imaging and blood samples collected from both renal veins for cytokine\u2010level measurements.\n              <jats:styled-content style=\"fixed-case\">EV<\/jats:styled-content>\n              s isolated from urine samples were characterized by imaging flow cytometry based on specific markers, including p16 (senescence marker), calyxin (podocytes), urate transporter 1 (proximal tubules), uromodulin (ascending limb of Henle's loop), and prominin\u20102 (distal tubules). Overall percentage of urinary p16+\n              <jats:styled-content style=\"fixed-case\">EV<\/jats:styled-content>\n              s was elevated in\n              <jats:styled-content style=\"fixed-case\">EH<\/jats:styled-content>\n              and renovascular hypertension patients compared with healthy volunteers and correlated inversely with renal function and directly with renal vein cytokine levels. Urinary levels of p16\n              <jats:sup>+<\/jats:sup>\n              \/urate transporter 1\n              <jats:sup>+<\/jats:sup>\n              were elevated in all hypertensive subjects compared with healthy volunteers, whereas p16\n              <jats:sup>+<\/jats:sup>\n              \/prominin\u20102\n              <jats:sup>+<\/jats:sup>\n              levels were elevated only in\n              <jats:styled-content style=\"fixed-case\">EH<\/jats:styled-content>\n              versus healthy volunteers and p16\n              <jats:sup>+<\/jats:sup>\n              \/uromodulin\n              <jats:sup>+<\/jats:sup>\n              in renovascular hypertension versus\n              <jats:styled-content style=\"fixed-case\">EH<\/jats:styled-content>\n              .\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Levels of p16\n              <jats:sup>+<\/jats:sup>\n              <jats:styled-content style=\"fixed-case\">EV<\/jats:styled-content>\n              s are elevated in urine of hypertensive patients and may reflect increased proximal tubular cellular senescence. In\n              <jats:styled-content style=\"fixed-case\">EH<\/jats:styled-content>\n              ,\n              <jats:styled-content style=\"fixed-case\">EV<\/jats:styled-content>\n              s originate also from distal tubules and in renovascular hypertension from Henle's loop. Hence, urinary\n              <jats:styled-content style=\"fixed-case\">EV<\/jats:styled-content>\n              s levels may be useful to identify intrarenal sites of cellular senescence.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.119.012584","type":"journal-article","created":{"date-parts":[[2019,6,1]],"date-time":"2019-06-01T09:08:06Z","timestamp":1559380086000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":49,"title":["Senescent Kidney Cells in Hypertensive Patients Release Urinary Extracellular Vesicles"],"prefix":"10.1161","volume":"8","author":[{"given":"Adrian","family":"Santelli","sequence":"first","affiliation":[{"name":"Division of Nephrology and Hypertension Mayo Clinic Rochester MN"},{"name":"Department of Physiopathology Hospital de Clinicas Montevideo Uruguay"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"In O.","family":"Sun","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension Mayo Clinic Rochester MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfonso","family":"Eirin","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension Mayo Clinic Rochester MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdelrhman M.","family":"Abumoawad","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension Mayo Clinic Rochester MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John R.","family":"Woollard","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension Mayo Clinic Rochester MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amir","family":"Lerman","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Diseases Mayo Clinic Rochester MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen\u00a0C.","family":"Textor","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension Mayo Clinic Rochester MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amrutesh S.","family":"Puranik","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension Mayo Clinic Rochester MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lilach O.","family":"Lerman","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension Mayo Clinic Rochester MN"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcna.2016.08.001"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.06460612"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2017-02694"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12279"},{"key":"e_1_3_1_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-06868-8"},{"key":"e_1_3_1_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature10600"},{"key":"e_1_3_1_8_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00030.2014"},{"key":"e_1_3_1_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.107.099432"},{"key":"e_1_3_1_10_2","first-page":"266","article-title":"Cell\u2010derived microvesicles and cancer","volume":"67","author":"van Doormaal FF","year":"2009","unstructured":"van Doormaal FF, Kleinjan A, Di Nisio M, Buller HR, Nieuwland R. 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