{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T05:31:36Z","timestamp":1791869496895,"version":"4.3.4"},"reference-count":40,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>\n                      A cardinal feature of Marfan syndrome is thoracic aortic aneurysm. The contribution of the renin-angiotensin system via AT1aR (Ang II [angiotensin II] receptor type 1a) to thoracic aortic aneurysm progression remains controversial because the beneficial effects of angiotensin receptor blockers have been ascribed to off-target effects. This study used genetic and pharmacological modes of attenuating angiotensin receptor and ligand, respectively, to determine their roles on thoracic aortic aneurysm in mice with fibrillin-1 haploinsufficiency (\n                      <jats:italic>Fbn1<\/jats:italic>\n                      <jats:sup>C1041G\/+<\/jats:sup>\n                      ).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Approach and Results:<\/jats:title>\n                    <jats:p>\n                      Thoracic aortic aneurysm in\n                      <jats:italic>Fbn1<\/jats:italic>\n                      <jats:sup>C1041G\/+<\/jats:sup>\n                      mice was found to be strikingly sexual dimorphic. Males displayed aortic dilation over 12 months while aortic dilation in\n                      <jats:italic>Fbn1<\/jats:italic>\n                      <jats:sup>C1041G\/+<\/jats:sup>\n                      females did not differ significantly from wild-type mice. To determine the role of AT1aR,\n                      <jats:italic>Fbn1<\/jats:italic>\n                      <jats:sup>C1041G\/+<\/jats:sup>\n                      mice that were either +\/+ or \u2212\/\u2212 for AT1aR were generated. AT1aR deletion reduced expansion of ascending aorta and aortic root diameter from 1 to 12 months of age in males. Medial thickening and elastin fragmentation were attenuated. An antisense oligonucleotide against angiotensinogen was administered to male\n                      <jats:italic>Fbn1<\/jats:italic>\n                      <jats:sup>C1041G\/+<\/jats:sup>\n                      mice to determine the effects of Ang II depletion. Antisense oligonucleotide against angiotensinogen administration attenuated dilation of the ascending aorta and aortic root and reduced extracellular remodeling. Aortic transcriptome analyses identified potential targets by which inhibition of the renin-angiotensin system reduced aortic dilation in\n                      <jats:italic>Fbn1<\/jats:italic>\n                      <jats:sup>C1041G\/+<\/jats:sup>\n                      mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>\n                      Deletion of AT1aR or inhibition of Ang II production exerted similar effects in attenuating pathologies in the proximal thoracic aorta of male\n                      <jats:italic>Fbn1<\/jats:italic>\n                      <jats:sup>C1041G\/+<\/jats:sup>\n                      mice. Inhibition of the renin-angiotensin system attenuated dysregulation of genes within the aorta related to pathology of\n                      <jats:italic>Fbn1<\/jats:italic>\n                      <jats:sup>C1041G\/+<\/jats:sup>\n                      mice.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/atvbaha.121.315715","type":"journal-article","created":{"date-parts":[[2021,8,19]],"date-time":"2021-08-19T05:02:23Z","timestamp":1629349343000},"page":"2538-2550","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":33,"title":["Deletion of AT1a (Angiotensin II Type 1a) Receptor or Inhibition of Angiotensinogen Synthesis Attenuates Thoracic Aortopathies in Fibrillin1\n                    <sup>C1041G\/+<\/sup>\n                    Mice"],"prefix":"10.1161","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2893-1523","authenticated-orcid":true,"given":"Jeff Z.","family":"Chen","sequence":"first","affiliation":[{"name":"Saha Cardiovascular Research Center (J.Z.C., H.S., D.Y., M.K., S.O.-U., J.J.M., M.K.F., D.A.H., M.B.S., H.S.L., A.D.), University of Kentucky, Lexington."},{"name":"Saha Aortic Center (J.Z.C., H.S., D.Y., M.K., S.O.-U., J.J.M., M.K.F., D.A.H., M.B.S., H.S.L., A.D.), University of Kentucky, Lexington."},{"name":"Department of Physiology (J.Z.C., H.S., M.B.S., H.S.L., A.D.), University of Kentucky, Lexington."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0017-6236","authenticated-orcid":true,"given":"Hisashi","family":"Sawada","sequence":"additional","affiliation":[{"name":"Saha Cardiovascular Research Center (J.Z.C., H.S., D.Y., M.K., S.O.-U., J.J.M., M.K.F., D.A.H., M.B.S., H.S.L., A.D.), University of Kentucky, Lexington."},{"name":"Saha Aortic Center (J.Z.C., H.S., D.Y., M.K., S.O.-U., J.J.M., M.K.F., D.A.H., M.B.S., H.S.L., A.D.), University of Kentucky, Lexington."},{"name":"Department of Physiology (J.Z.C., H.S., M.B.S., H.S.L., A.D.), University of Kentucky, Lexington."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6433-5032","authenticated-orcid":true,"given":"Dien","family":"Ye","sequence":"additional","affiliation":[{"name":"Saha Cardiovascular Research Center (J.Z.C., H.S., D.Y., M.K., S.O.-U., J.J.M., M.K.F., D.A.H., M.B.S., H.S.L., A.D.), University of Kentucky, Lexington."},{"name":"Saha Aortic Center (J.Z.C., H.S., D.Y., M.K., S.O.-U., J.J.M., M.K.F., D.A.H., M.B.S., H.S.L., A.D.), University of Kentucky, Lexington."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuriko","family":"Katsumata","sequence":"additional","affiliation":[{"name":"Department of Biostatistics (Y.K.), University of Kentucky, Lexington."},{"name":"Sanders-Brown Center on Aging (Y.K.), University of Kentucky, Lexington."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayoshi","family":"Kukida","sequence":"additional","affiliation":[{"name":"Saha Cardiovascular Research Center (J.Z.C., H.S., D.Y., M.K., S.O.-U., J.J.M., M.K.F., D.A.H., M.B.S., H.S.L., A.D.), University of Kentucky, Lexington."},{"name":"Saha Aortic Center (J.Z.C., H.S., D.Y., M.K., S.O.-U., J.J.M., M.K.F., D.A.H., M.B.S., H.S.L., A.D.), University of Kentucky, Lexington."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoko","family":"Ohno-Urabe","sequence":"additional","affiliation":[{"name":"Saha Cardiovascular Research Center (J.Z.C., H.S., D.Y., M.K., S.O.-U., J.J.M., M.K.F., D.A.H., M.B.S., H.S.L., A.D.), University of Kentucky, Lexington."},{"name":"Saha Aortic Center (J.Z.C., H.S., D.Y., M.K., S.O.-U., J.J.M., M.K.F., D.A.H., M.B.S., H.S.L., A.D.), University of Kentucky, Lexington."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica 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Center (J.Z.C., H.S., D.Y., M.K., S.O.-U., J.J.M., M.K.F., D.A.H., M.B.S., H.S.L., A.D.), University of Kentucky, Lexington."},{"name":"Saha Aortic Center (J.Z.C., H.S., D.Y., M.K., S.O.-U., J.J.M., M.K.F., D.A.H., M.B.S., H.S.L., A.D.), University of Kentucky, Lexington."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary B.","family":"Sheppard","sequence":"additional","affiliation":[{"name":"Saha Cardiovascular Research Center (J.Z.C., H.S., D.Y., M.K., S.O.-U., J.J.M., M.K.F., D.A.H., M.B.S., H.S.L., A.D.), University of Kentucky, Lexington."},{"name":"Saha Aortic Center (J.Z.C., H.S., D.Y., M.K., S.O.-U., J.J.M., M.K.F., D.A.H., M.B.S., H.S.L., A.D.), University of Kentucky, Lexington."},{"name":"Department of Physiology (J.Z.C., H.S., M.B.S., H.S.L., A.D.), University of Kentucky, Lexington."},{"name":"Department of Family and Community Medicine (M.B.S.), University of Kentucky, Lexington."},{"name":"Department of Surgery (M.B.S.), University of Kentucky, 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