{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T12:08:15Z","timestamp":1791720495666,"version":"4.3.4"},"reference-count":61,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,6,24]],"date-time":"2020-06-24T00:00:00Z","timestamp":1592956800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2020,6,24]],"date-time":"2020-06-24T00:00:00Z","timestamp":1592956800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.tandfonline.com"],"crossmark-restriction":true},"short-container-title":["J of Extracellular Vesicle"],"published-print":{"date-parts":[[2020,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>\n                      The prevalence of arterial stiffness and hypertension increases with age. This study investigates the effect of induced pluripotent mesenchymal stem cell\u2010derived extracellular vesicles (EVs) on ageing\u2010associated arterial stiffness and hypertension. EVs were collected and purified from induced pluripotent stem cell\u2010derived mesenchymal stem cells (iPS\u2010MSCs). Young and old male C57BL\/6\u00a0mice were used. Mice in the EVs group were injected\n                      <jats:italic>via<\/jats:italic>\n                      tail vein once a week for four weeks (18 x 10\n                      <jats:sup>6<\/jats:sup>\n                      EVs\/mouse\/injection). Blood pressure (BP) was measured using the tail\u2010cuff method and validated by direct cannulation. Pulse wave velocity (PWV) was measured using a Doppler workstation. PWV and BP were increased significantly in the old mice, indicating arterial stiffness and hypertension. Intravenous administration of EVs significantly attenuated ageing\u2010related arterial stiffness and hypertension, while enhancing endothelium\u2010dependent vascular relaxation and arterial compliance in the old EVs mice. Elastin degradation and collagen I deposition (fibrosis) were increased in aortas of the old mice, but EVs substantially improved ageing\u2010associated structural remodelling. Mechanistically, EVs abolished downregulation of sirtuin type 1 (SIRT1), and endothelial nitric oxide synthase (eNOS) protein expression in aortas of the older mice. In cultured human aortic endothelial cells, EVs promoted the expression of SIRT1, AMP\u2010activated protein kinase alpha (AMPK\u03b1), and eNOS. In conclusion, iPS\u2010MSC\u2010derived EVs attenuated ageing\u2010associated vascular endothelial dysfunction, arterial stiffness, and hypertension, likely\n                      <jats:italic>via<\/jats:italic>\n                      activation of the SIRT1\u2010AMPK\u03b1\u2010eNOS pathway and inhibition of MMPs and elastase. Thus, EVs mitigate arterial ageing. This finding also sheds light into the therapeutic potential of EVs for ageing\u2010related vascular diseases.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Abbreviations<\/jats:title>\n                    <jats:p>EV: Extracellular vesicles; iPS: induced pluripotent stem cell; MSC: mesenchymal stem cell; AMPK\u03b1: AMP activated protein kinase \u03b1; eNOS: endothelial nitric oxide synthase; Sirt1: sirtuin 1; JNC7: Seventh Report of the Joint National Committee; CVD: cardiovascular disease; PWV: pulse wave velocity; BP: blood pressure; SNP: sodium nitroprusside<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1080\/20013078.2020.1783869","type":"journal-article","created":{"date-parts":[[2020,6,24]],"date-time":"2020-06-24T05:40:01Z","timestamp":1592977201000},"update-policy":"https:\/\/doi.org\/10.1080\/tandf_crossmark_01","source":"Crossref","is-referenced-by-count":89,"title":["Stem cell\u2010derived extracellular vesicles mitigate ageing\u2010associated arterial stiffness and hypertension"],"prefix":"10.1002","volume":"9","author":[{"given":"Rui","family":"Feng","sequence":"first","affiliation":[{"name":"Department of Cardiology The First Affiliated Hospital of Chongqing Medical University Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mujib","family":"Ullah","sequence":"additional","affiliation":[{"name":"Department of Physiology College of Medicine University of Tennessee Health Sciences Center Memphis TN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Physiology College of Medicine University of Tennessee Health Sciences Center Memphis TN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quaisar","family":"Ali","sequence":"additional","affiliation":[{"name":"Department of Physiology College of Medicine University of Tennessee Health Sciences Center Memphis TN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Physiology College of Medicine University of Tennessee Health Sciences Center Memphis TN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongjie","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Physiology College of Medicine University of Tennessee Health Sciences Center Memphis TN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,6,24]]},"reference":[{"key":"e_1_2_11_2_2","first-page":"1","article-title":"Age at death of major cardiovascular diseases in 13 cohorts. The seven countries study of cardiovascular diseases 45\u2010year follow\u2010up","volume":"74","author":"Menotti A","year":"2018","journal-title":"Acta Cardiol"},{"key":"e_1_2_11_3_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2018.00018"},{"key":"e_1_2_11_4_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2013.284427"},{"key":"e_1_2_11_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYP.0000000000000033"},{"key":"e_1_2_11_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2010.12.017"},{"key":"e_1_2_11_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12265-012-9349-8"},{"key":"e_1_2_11_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.114.03617"},{"key":"e_1_2_11_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.117.311703"},{"key":"e_1_2_11_10_2","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.03000315"},{"key":"e_1_2_11_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.109.143024"},{"key":"e_1_2_11_12_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.mnh.0000441153.40072.e0"},{"key":"e_1_2_11_13_2","doi-asserted-by":"publisher","DOI":"10.2174\/15701611113119990147"},{"key":"e_1_2_11_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11883-013-0387-8"},{"key":"e_1_2_11_15_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.hjh.0000170384.38708.b7"},{"key":"e_1_2_11_16_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.117.310752"},{"key":"e_1_2_11_17_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.117.309681"},{"key":"e_1_2_11_18_2","doi-asserted-by":"publisher","DOI":"10.1113\/JP272112"},{"key":"e_1_2_11_19_2","doi-asserted-by":"publisher","DOI":"10.1113\/JP271336"},{"key":"e_1_2_11_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2009.03.005"},{"key":"e_1_2_11_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virusres.2017.04.007"},{"key":"e_1_2_11_22_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.110.233163"},{"key":"e_1_2_11_23_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12020-012-9839-0"},{"key":"e_1_2_11_24_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201212113"},{"key":"e_1_2_11_25_2","doi-asserted-by":"publisher","DOI":"10.1001\/2012.jama.10503"},{"key":"e_1_2_11_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2016.12.023"},{"key":"e_1_2_11_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehy012"},{"key":"e_1_2_11_28_2","doi-asserted-by":"publisher","DOI":"10.1159\/000480317"},{"key":"e_1_2_11_29_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-013-1110-5"},{"key":"e_1_2_11_30_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.116.08184"},{"key":"e_1_2_11_31_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.115.06825"},{"key":"e_1_2_11_32_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.115.06033"},{"key":"e_1_2_11_33_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2013101033"},{"key":"e_1_2_11_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/ajh.2008.301"},{"key":"e_1_2_11_35_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.116.07709"},{"key":"e_1_2_11_36_2","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12762"},{"key":"e_1_2_11_37_2","doi-asserted-by":"crossref","first-page":"1615","DOI":"10.1007\/s00109-019-01841-6","article-title":"Autophagy plays a critical role in Klotho gene deficiency\u2010induced arterial stiffening and hypertension","volume":"97","author":"Chen K","year":"2019","journal-title":"J Mol Med (Berl)"},{"key":"e_1_2_11_38_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.114.302113"},{"key":"e_1_2_11_39_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2014.285338"},{"key":"e_1_2_11_40_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0059682"},{"key":"e_1_2_11_41_2","doi-asserted-by":"publisher","DOI":"10.2337\/db14-0632"},{"key":"e_1_2_11_42_2","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/gly261"},{"key":"e_1_2_11_43_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.117.10560"},{"key":"e_1_2_11_44_2","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12494"},{"key":"e_1_2_11_45_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.109.134320"},{"key":"e_1_2_11_46_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gt.3302768"},{"key":"e_1_2_11_47_2","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2012.078"},{"key":"e_1_2_11_48_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.113.01445"},{"key":"e_1_2_11_49_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehl254"},{"key":"e_1_2_11_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2007.10.065"},{"key":"e_1_2_11_51_2","doi-asserted-by":"publisher","DOI":"10.1098\/rsif.2012.1004"},{"key":"e_1_2_11_52_2","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2015.00112"},{"key":"e_1_2_11_53_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.116.308895"},{"key":"e_1_2_11_54_2","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s13287-017-0746-4","article-title":"Stem cells and anti\u2010aging genes: double\u2010edged sword\u2010do the same job of life extension","volume":"9","author":"Ullah M","year":"2018","journal-title":"Stem Cell Res Ther"},{"key":"e_1_2_11_55_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2016.07.044"},{"key":"e_1_2_11_56_2","article-title":"Stem cell\u2010derived exosomes: A promising strategy for fracture healing","volume":"50","author":"Hao ZC","year":"2017","journal-title":"Cell Prolif"},{"key":"e_1_2_11_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2014.10.053"},{"key":"e_1_2_11_58_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvy009"},{"key":"e_1_2_11_59_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00003.2017"},{"key":"e_1_2_11_60_2","doi-asserted-by":"publisher","DOI":"10.1111\/tri.12445"},{"key":"e_1_2_11_61_2","doi-asserted-by":"publisher","DOI":"10.1038\/aps.2016.35"},{"key":"e_1_2_11_62_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18040776"}],"container-title":["Journal of Extracellular Vesicles"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/isevjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1080\/20013078.2020.1783869","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/isevjournals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1080\/20013078.2020.1783869","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/isevjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1080\/20013078.2020.1783869","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T10:30:54Z","timestamp":1781692254000},"score":1,"resource":{"primary":{"URL":"https:\/\/isevjournals.onlinelibrary.wiley.com\/doi\/10.1080\/20013078.2020.1783869"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,24]]},"references-count":61,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,9]]}},"alternative-id":["10.1080\/20013078.2020.1783869"],"URL":"https:\/\/doi.org\/10.1080\/20013078.2020.1783869","archive":["Portico"],"relation":{},"ISSN":["2001-3078","2001-3078"],"issn-type":[{"value":"2001-3078","type":"print"},{"value":"2001-3078","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,24]]},"assertion":[{"value":"The publishing and review policy for this title is described in its Aims & Scope.","order":1,"name":"peerreview_statement","label":"Peer Review Statement"},{"value":"http:\/\/www.tandfonline.com\/action\/journalInformation?show=aimsScope&journalCode=zjev20","URL":"http:\/\/www.tandfonline.com\/action\/journalInformation?show=aimsScope&journalCode=zjev20","order":2,"name":"aims_and_scope_url","label":"Aim & Scope"},{"value":"2019-08-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-02-01","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-04-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-06-24","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"1783869"}}