{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T01:41:12Z","timestamp":1773798072002,"version":"3.50.1"},"reference-count":45,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2023,2,7]]},"abstract":"<jats:sec sec-type=\"background\" xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Angiotensin II type 1 receptor blockers (ARBs) have been shown to limit the growth of abdominal aortic aneurysm (AAA), but their efficacy is controversial. This study aimed to investigate the molecular mechanism underlying the protective effect of ARBs against AAA progression.<\/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              Olmesartan, an ARB, was administered to wild\u2010type and\n              <jats:italic>osteoprotegerin<\/jats:italic>\n              \u2010knockout (\n              <jats:italic>Opg<\/jats:italic>\n              \u2010KO) mice starting 2\u2009weeks before direct application of CaCl\n              <jats:sub>2<\/jats:sub>\n              to aortas to induce AAA. The protective effect of olmesartan against AAA in wild\u2010type and\n              <jats:italic>Opg<\/jats:italic>\n              \u2010KO mice was compared at 6\u2009weeks after AAA induction. Olmesartan prevented AAA progression in\n              <jats:italic>Opg<\/jats:italic>\n              \u2010KO mice, including excessive aortic dilatation and collapse of tunica media, but not in wild\u2010type mice. Deficiency of the\n              <jats:italic>Opg<\/jats:italic>\n              gene is known to cause excessive activation of the tumor necrosis factor\u2013related apoptosis\u2010inducing ligand\u2013induced c\u2010Jun N\u2010terminal kinase\/matrix metalloproteinase 9 pathway, resulting in prolonged AAA progression. Olmesartan attenuated the upregulation of phosphorylated c\u2010Jun N\u2010terminal kinase and matrix metalloproteinase 9 expression in the aortic wall of\n              <jats:italic>Opg<\/jats:italic>\n              \u2010KO mice. In cultured vascular smooth muscle cells, tumor necrosis factor\u2013related apoptosis\u2010inducing ligand\u2013induced c\u2010Jun N\u2010terminal kinase phosphorylation and matrix metalloproteinase 9 expression were inhibited by angiotensin (1\u20137), the circulating levels of which are increased by ARBs. Furthermore, administering an angiotensin (1\u20137) antagonist to\n              <jats:italic>Opg<\/jats:italic>\n              \u2010KO mice diminished the protective effect of olmesartan against AAA progression.\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              Olmesartan prevented AAA progression in\n              <jats:italic>Opg\u2010<\/jats:italic>\n              KO mice by upregulating angiotensin (1\u20137), suggesting that angiotensin (1\u20137) may be a key factor that mediates the protective effect of ARBs.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.122.027589","type":"journal-article","created":{"date-parts":[[2023,1,31]],"date-time":"2023-01-31T11:10:55Z","timestamp":1675163455000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":10,"title":["Angiotensin II Type 1 Receptor Blocker Prevents Abdominal Aortic Aneurysm Progression in Osteoprotegerin\u2010Deficient Mice via Upregulation of Angiotensin (1\u20137)"],"prefix":"10.1161","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3845-828X","authenticated-orcid":false,"given":"Kohei","family":"Karasaki","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Physiology and Medicine, Graduate School of Biomedical and Health Sciences Hiroshima University Hiroshima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7216-3066","authenticated-orcid":false,"given":"Hiroki","family":"Kokubo","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Physiology and Medicine, Graduate School of Biomedical and Health Sciences Hiroshima University Hiroshima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Batmunkh","family":"Bumdelger","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Physiology and Medicine, Graduate School of Biomedical and Health Sciences Hiroshima University Hiroshima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nobuchika","family":"Kaji","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Physiology and Medicine, Graduate School of Biomedical and Health Sciences Hiroshima University Hiroshima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3533-6228","authenticated-orcid":false,"given":"Chiemi","family":"Sakai","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Physiology and Medicine, Graduate School of Biomedical and Health Sciences Hiroshima University Hiroshima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0881-0182","authenticated-orcid":false,"given":"Mari","family":"Ishida","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Physiology and Medicine, Graduate School of Biomedical and Health Sciences Hiroshima University Hiroshima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masao","family":"Yoshizumi","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Physiology and Medicine, Graduate School of Biomedical and Health Sciences Hiroshima University Hiroshima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-018-0030-7"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejvs.2011.06.043"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvs.2015.01.042"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/joim.12958"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci7818"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/eci.12173"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvs.2010.02.012"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/atvbaha.114.304428"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1253\/circj.CJ-16-0902"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvs.2017.09.007"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamacardio.2020.3524"},{"key":"e_1_3_2_13_2","first-page":"703","article-title":"Inhibition of experimental abdominal aortic aneurysm in a rat model by the angiotensin receptor blocker valsartan","volume":"22","author":"Fujiwara Y","year":"2008","unstructured":"Fujiwara Y, Shiraya S, Miyake T, Yamakawa S, Aoki M, Makino H, Nishimura M, Morishita R. 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