{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T14:22:02Z","timestamp":1792678922247,"version":"4.5.0"},"reference-count":71,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2018,5]]},"abstract":"<jats:sec>\n            <jats:title>Objective\u2014<\/jats:title>\n            <jats:p>\n              Thoracic aortic aneurysm and dissection (TAAD) are severe vascular conditions. Dysfunctional transforming growth factor-\u03b2 (TGF-\u03b2) signaling in vascular smooth muscle cells and elevated angiotensin II (AngII) levels are implicated in the development of TAAD. In this study, we investigated whether these 2 factors lead to TAAD in a mouse model and explored the possibility of using microRNA-21 (\n              <jats:italic>miR-21<\/jats:italic>\n              ) for the treatment of TAAD.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results\u2014<\/jats:title>\n            <jats:p>\n              TAAD was developed in\n              <jats:italic>Smad3<\/jats:italic>\n              (mothers against decapentaplegic homolog 3) heterozygous (S3\n              <jats:sup>+\/\u2212<\/jats:sup>\n              ) mice infused with AngII. We found that p-ERK (phosphorylated extracellular regulated protein kinases)\u2013 and p-JNK (phosphorylated c-Jun N-terminal kinase)\u2013associated\n              <jats:italic>miR-21<\/jats:italic>\n              was higher in TAAD lesions. We hypothesize that downregulation of\n              <jats:italic>miR-21<\/jats:italic>\n              mitigate TAAD formation. However,\n              <jats:italic>Smad3<\/jats:italic>\n              <jats:sup>+\/\u2212<\/jats:sup>\n              <jats:italic>:miR-21<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              (S3\n              <jats:sup>+\/\u2212<\/jats:sup>\n              21\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              ) mice exhibited conspicuous TAAD formation after AngII infusion. The vascular wall was dilated, and aortic rupture occurred within 23 days during AngII infusion. We then examined canonical and noncanonical TGF-\u03b2 signaling and found that\n              <jats:italic>miR-21<\/jats:italic>\n              knockout in S3\n              <jats:sup>+\/\u2212<\/jats:sup>\n              mice increased SMAD7 and suppressed canonical TGF-\u03b2 signaling. Vascular smooth muscle cells lacking TGF-\u03b2 signals tended to switch from a contractile to a synthetic phenotype. The silencing of\n              <jats:italic>Smad7<\/jats:italic>\n              with lentivirus prevented AngII-induced TAAD formation in S3\n              <jats:sup>+\/\u2212<\/jats:sup>\n              21\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>\n              Our study demonstrated that\n              <jats:italic>miR-21<\/jats:italic>\n              knockout exacerbated AngII-induced TAAD formation in mice, which was associated with TGF-\u03b2 signaling dysfunction. Therapeutic strategies targeting TAAD should consider unexpected side effects associated with alterations in TGF-\u03b2 signaling.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.117.310694","type":"journal-article","created":{"date-parts":[[2018,3,8]],"date-time":"2018-03-08T10:00:16Z","timestamp":1520503216000},"page":"1086-1101","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":71,"title":["MicroRNA-21 Knockout Exacerbates Angiotensin II\u2013Induced Thoracic Aortic Aneurysm and Dissection in Mice With Abnormal Transforming Growth Factor-\u03b2\u2013SMAD3 Signaling"],"prefix":"10.1161","volume":"38","author":[{"given":"Xiaofan","family":"Huang","sequence":"first","affiliation":[{"name":"From the Department of Cardiovascular Surgery, Union Hospital (X.H., Z.Y., J.C., J.W., P.D., K.W., C.W., X.D., J.X.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhang","family":"Yue","sequence":"additional","affiliation":[{"name":"From the Department of Cardiovascular Surgery, Union Hospital (X.H., Z.Y., J.C., J.W., P.D., K.W., C.W., X.D., J.X.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Wu","sequence":"additional","affiliation":[{"name":"From the Department of Cardiovascular Surgery, Union Hospital (X.H., Z.Y., J.C., J.W., P.D., K.W., C.W., X.D., J.X.)"},{"name":"Key Laboratory for Molecular Diagnosis of Hubei Province, Central Hospital of Wuhan (J.W.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiuling","family":"Chen","sequence":"additional","affiliation":[{"name":"From the Department of Cardiovascular Surgery, Union Hospital (X.H., Z.Y., J.C., J.W., P.D., K.W., C.W., X.D., J.X.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sihua","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Union Hospital (S.W.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Wu","sequence":"additional","affiliation":[{"name":"Central Laboratory, Central Hospital of Wuhan (J.W.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linyun","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Anesthesia, Central Hospital of Wuhan (L.R.), Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anchen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Central Hospital of Wuhan (A.Z., P.Y.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Deng","sequence":"additional","affiliation":[{"name":"From the Department of Cardiovascular Surgery, Union Hospital (X.H., Z.Y., J.C., J.W., P.D., K.W., C.W., X.D., J.X.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Wang","sequence":"additional","affiliation":[{"name":"From the Department of Cardiovascular Surgery, Union Hospital (X.H., Z.Y., J.C., J.W., P.D., K.W., C.W., X.D., J.X.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuangyan","family":"Wu","sequence":"additional","affiliation":[{"name":"From the Department of Cardiovascular Surgery, Union Hospital (X.H., Z.Y., J.C., J.W., P.D., K.W., C.W., X.D., J.X.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangchao","family":"Ding","sequence":"additional","affiliation":[{"name":"From the Department of Cardiovascular Surgery, Union Hospital (X.H., Z.Y., J.C., J.W., P.D., K.W., C.W., X.D., J.X.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Central Hospital of Wuhan (A.Z., P.Y.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahong","family":"Xia","sequence":"additional","affiliation":[{"name":"From the Department of Cardiovascular Surgery, Union Hospital (X.H., Z.Y., J.C., J.W., P.D., K.W., C.W., X.D., J.X.)"},{"name":"Department of Cardiovascular Surgery, Central Hospital of Wuhan (J.X.)"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.107.702720"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrcardio.2010.187"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.112.097097"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a015909"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature10145"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2013.01.002"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI73906"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1124287"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1192152"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI69666"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.114.305150"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1404731"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1103735108"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/18.5.1280"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.117.309524"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI7818"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI67356"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000153088.15433.8f"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2010.62"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3003441"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1192149"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.115.308040"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature07086"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2013.374"},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000085631.76095.64"},{"key":"e_1_3_5_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1335"},{"key":"e_1_3_5_28_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvr280"},{"key":"e_1_3_5_29_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.114.304412"},{"key":"e_1_3_5_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature07511"},{"key":"e_1_3_5_31_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.114.304877"},{"key":"e_1_3_5_32_2","doi-asserted-by":"publisher","DOI":"10.1042\/CS20090372"},{"key":"e_1_3_5_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2010.01.042"},{"key":"e_1_3_5_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bmt.1703766"},{"key":"e_1_3_5_35_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.109.213900"},{"key":"e_1_3_5_36_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.genom.8.080706.092303"},{"key":"e_1_3_5_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2010.10.006"},{"key":"e_1_3_5_38_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.111.261743"},{"key":"e_1_3_5_39_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddt167"},{"key":"e_1_3_5_40_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvq230"},{"key":"e_1_3_5_41_2","doi-asserted-by":"publisher","DOI":"10.1093\/icvts\/ivv074"},{"key":"e_1_3_5_42_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.16.10948"},{"key":"e_1_3_5_43_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvq291"},{"key":"e_1_3_5_44_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.116.303229"},{"key":"e_1_3_5_45_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.116.308261"},{"key":"e_1_3_5_46_2","doi-asserted-by":"publisher","DOI":"10.2478\/v10034-012-0019-6"},{"key":"e_1_3_5_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtcvs.2012.12.027"},{"key":"e_1_3_5_48_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00595.2011"},{"key":"e_1_3_5_49_2","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00044.2011"},{"key":"e_1_3_5_50_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M708137200"},{"key":"e_1_3_5_51_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.303156"},{"key":"e_1_3_5_52_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.109.202028"},{"key":"e_1_3_5_53_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.111.234286"},{"key":"e_1_3_5_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2014.05.018"},{"key":"e_1_3_5_55_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00413.2009"},{"key":"e_1_3_5_56_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.81.4.600"},{"key":"e_1_3_5_57_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.hyp.13.4.305"},{"key":"e_1_3_5_58_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI82337"},{"key":"e_1_3_5_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2014.05.014"},{"key":"e_1_3_5_60_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.113.000269"},{"key":"e_1_3_5_61_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI74347"},{"key":"e_1_3_5_62_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.4A1014-489R"},{"key":"e_1_3_5_63_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep10180"},{"key":"e_1_3_5_64_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.744"},{"key":"e_1_3_5_65_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.111.248161"},{"key":"e_1_3_5_66_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2011-100382"},{"key":"e_1_3_5_67_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0153811"},{"key":"e_1_3_5_68_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12471-014-0622-0"},{"key":"e_1_3_5_69_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1253026"},{"key":"e_1_3_5_70_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.115.306573"},{"key":"e_1_3_5_71_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0059002"},{"key":"e_1_3_5_72_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20100035"}],"container-title":["Arteriosclerosis, Thrombosis, and Vascular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/ATVBAHA.117.310694","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,12]],"date-time":"2024-05-12T23:20:35Z","timestamp":1715556035000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/ATVBAHA.117.310694"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,5]]},"references-count":71,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2018,5]]}},"alternative-id":["10.1161\/ATVBAHA.117.310694"],"URL":"https:\/\/doi.org\/10.1161\/atvbaha.117.310694","relation":{},"ISSN":["1079-5642","1524-4636"],"issn-type":[{"value":"1079-5642","type":"print"},{"value":"1524-4636","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,5]]},"assertion":[{"value":"2017-09-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-02-19","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-03-08","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}