{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T01:35:09Z","timestamp":1776130509075,"version":"3.50.1"},"reference-count":59,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"16","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2021,8,17]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Thoracic aortic aneurysms (TAAs) occur because of abnormal remodeling of aortic extracellular matrix and are accompanied by the emergence of proteolytically active myofibroblasts. The microRNA miR\u2010133a regulates cellular phenotypes and is reduced in clinical TAA specimens. This study tested the hypothesis that miR\u2010133a modulates aortic fibroblast phenotype, and overexpression by lentivirus attenuates the development of TAA in a murine model.<\/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\">TAA was induced in mice. Copy number of miR\u2010133a was reduced in TAA tissue and linear regression analysis confirmed an inverse correlation between aortic diameter and miR\u2010133a. Analyses of phenotypic markers revealed an mRNA expression profile consistent with myofibroblasts in TAA tissue. Fibroblasts were isolated from the thoracic aortae of mice with\/without TAA. When compared with controls, miR\u2010133a was reduced, migration was increased, adhesion was reduced, and the ability to contract a collagen disk was increased. Overexpression\/knockdown of miR\u2010133a controlled these phenotypes. After TAA induction in mice, a single tail\u2010vein injection of either miR\u2010133a overexpression or scrambled sequence (control) lentivirus was performed. Overexpression of miR\u2010133a attenuated TAA development. The pro\u2010protein convertase furin was confirmed to be a target of miR\u2010133a by luciferase reporter assay. Furin was elevated in this murine model of TAA and repressed by miR\u2010133a replacement in vivo resulting in reduced proteolytic activation.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">miR\u2010133a regulates aortic fibroblast phenotype and over\u2010expression prevented the development of TAA in a murine model. These findings suggest that stable alterations in aortic fibroblasts are associated with development of TAA and regulation by miR\u2010133a may lead to a novel therapeutic strategy.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.120.019862","type":"journal-article","created":{"date-parts":[[2021,8,13]],"date-time":"2021-08-13T09:20:30Z","timestamp":1628846430000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":14,"title":["miR\u2010133a Replacement Attenuates Thoracic Aortic Aneurysm in Mice"],"prefix":"10.1161","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8117-0591","authenticated-orcid":false,"given":"Adam W.","family":"Akerman","sequence":"first","affiliation":[{"name":"Division of Cardiothoracic Surgery Department of Surgery University of North Carolina Chapel Hill NC"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth N.","family":"Collins","sequence":"additional","affiliation":[{"name":"Division of Cardiothoracic Surgery Department of Surgery University of North Carolina Chapel Hill NC"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew R.","family":"Peterson","sequence":"additional","affiliation":[{"name":"Division of Cardiothoracic Surgery Department of Surgery University of North Carolina Chapel Hill NC"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4773-5712","authenticated-orcid":false,"given":"Lauren B.","family":"Collins","sequence":"additional","affiliation":[{"name":"Division of Cardiothoracic Surgery Department of Surgery University of North Carolina Chapel Hill NC"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4578-8431","authenticated-orcid":false,"given":"Jessica K.","family":"Harrison","sequence":"additional","affiliation":[{"name":"Division of Cardiothoracic Surgery Department of Surgery University of North Carolina Chapel Hill NC"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0870-5748","authenticated-orcid":false,"given":"Amari","family":"DeVaughn","sequence":"additional","affiliation":[{"name":"Division of Cardiothoracic Surgery Department of Surgery University of North Carolina Chapel Hill NC"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaleel M.","family":"Townsend","sequence":"additional","affiliation":[{"name":"Division of Cardiothoracic Surgery Department of Surgery University of North Carolina Chapel Hill NC"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7677-2870","authenticated-orcid":false,"given":"Rebecca L.","family":"Vanbuskirk","sequence":"additional","affiliation":[{"name":"Division of Cardiothoracic Surgery Department of Surgery University of North Carolina Chapel Hill NC"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica","family":"Riopedre\u2010Maqueira","sequence":"additional","affiliation":[{"name":"Division of Cardiothoracic Surgery Department of Surgery University of North Carolina Chapel Hill NC"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ailet","family":"Reyes","sequence":"additional","affiliation":[{"name":"Division of Cardiothoracic Surgery Department of Surgery University of North Carolina Chapel Hill NC"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5413-9268","authenticated-orcid":false,"given":"Joyce E.","family":"Oh","sequence":"additional","affiliation":[{"name":"Division of Cardiothoracic Surgery Department of Surgery University of North Carolina Chapel Hill NC"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles M.","family":"Raybuck","sequence":"additional","affiliation":[{"name":"Division of Cardiothoracic Surgery Department of Surgery University of North Carolina Chapel Hill NC"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey A.","family":"Jones","sequence":"additional","affiliation":[{"name":"Division of Cardiothoracic Surgery Department of Surgery Medical University of South Carolina Charleston SC"},{"name":"Research Service Ralph H. 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