{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T04:24:04Z","timestamp":1790396644729,"version":"4.1.0"},"reference-count":76,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2022,12,8]],"date-time":"2022-12-08T00:00:00Z","timestamp":1670457600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Libin Cardiovascular Institute, Cumming School of Medicine"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Thoracic aortic aneurysm (TAA) involves extracellular matrix (ECM) remodeling of the aortic wall, leading to reduced biomechanical support with risk of aortic dissection and rupture. Activation of the renin-angiotensin system, and resultant angiotensin (Ang) II synthesis, is critically involved in the onset and progression of TAA. The current study investigated the effects of angiotensin (Ang) 1-7 on a murine model of TAA. Male 8\u201310-week-old ApoEKO mice were infused with Ang II (1.44 mg\/kg\/day) and treated with Ang 1-7 (0.576 mg\/kg\/day). ApoEKO mice developed advanced TAA in response to four weeks of Ang II infusion. Echocardiographic and histological analyses demonstrated increased aortic dilatation, excessive structural remodelling, perivascular fibrosis, and inflammation in the thoracic aorta. Ang 1-7 infusion led to attenuation of pathological phenotypic alterations associated with Ang II-induced TAA. Smooth muscle cells (SMCs) isolated from adult murine thoracic aorta exhibited excessive mitochondrial fission, oxidative stress, and hyperproliferation in response to Ang II. Treatment with Ang 1-7 resulted in inhibition of mitochondrial fragmentation, ROS generation, and hyperproliferation. Gene expression profiling used for characterization of the contractile and synthetic phenotypes of thoracic aortic SMCs revealed preservation of the contractile phenotype with Ang 1-7 treatment. In conclusion, Ang 1-7 prevented Ang II-induced vascular remodeling and the development of TAA. Enhancing Ang 1-7 actions may provide a novel therapeutic strategy to prevent or delay the progression of TAA.<\/jats:p>","DOI":"10.3390\/ijms232415566","type":"journal-article","created":{"date-parts":[[2022,12,9]],"date-time":"2022-12-09T01:51:26Z","timestamp":1670550686000},"page":"15566","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Attenuation of Smooth Muscle Cell Phenotypic Switching by Angiotensin 1-7 Protects against Thoracic Aortic Aneurysm"],"prefix":"10.3390","volume":"23","author":[{"given":"Anshul S.","family":"Jadli","sequence":"first","affiliation":[{"name":"Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada"},{"name":"Libin Cardiovascular Institute, University of Calgary, Calgary, AB T2N 4N1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noura N.","family":"Ballasy","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada"},{"name":"Libin Cardiovascular Institute, University of Calgary, Calgary, AB T2N 4N1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karina P.","family":"Gomes","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada"},{"name":"Libin Cardiovascular Institute, University of Calgary, Calgary, AB T2N 4N1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cameron D. A.","family":"Mackay","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada"},{"name":"Libin Cardiovascular Institute, University of Calgary, Calgary, AB T2N 4N1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan","family":"Meechem","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada"},{"name":"Libin Cardiovascular Institute, University of Calgary, Calgary, AB T2N 4N1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2996-7496","authenticated-orcid":false,"given":"Tishani Methsala","family":"Wijesuriya","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada"},{"name":"Libin Cardiovascular Institute, University of Calgary, Calgary, AB T2N 4N1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darrell","family":"Belke","sequence":"additional","affiliation":[{"name":"Libin Cardiovascular Institute, University of Calgary, Calgary, AB T2N 4N1, Canada"},{"name":"Section of Cardiac Surgery, Department of Cardiac Sciences, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Thompson","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada"},{"name":"Libin Cardiovascular Institute, University of Calgary, Calgary, AB T2N 4N1, Canada"},{"name":"Alberta Children\u2019s Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0658-9381","authenticated-orcid":false,"given":"Paul W. M.","family":"Fedak","sequence":"additional","affiliation":[{"name":"Libin Cardiovascular Institute, University of Calgary, Calgary, AB T2N 4N1, Canada"},{"name":"Section of Cardiac Surgery, Department of Cardiac Sciences, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vaibhav B.","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada"},{"name":"Libin Cardiovascular Institute, University of Calgary, Calgary, AB T2N 4N1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/j.jvs.2012.04.053","article-title":"Natural history of thoracic aortic aneurysms","volume":"56","author":"Kuzmik","year":"2012","journal-title":"J. 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