{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T15:16:52Z","timestamp":1761059812920},"reference-count":47,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2014,12]]},"abstract":"<jats:sec>\n            <jats:title>Objective\u2014<\/jats:title>\n            <jats:p>\n              Mounting evidence links osteoprotegerin with cardiovascular disease. Elevated serum and aortic tissue osteoprotegerin are associated with the presence and growth of abdominal aortic aneurysm in humans; however, a role for osteoprotegerin in abdominal aortic aneurysm pathogenesis remains to be shown. We examined the functional significance of osteoprotegerin in aortic aneurysm using an\n              <jats:italic>Opg<\/jats:italic>\n              -deficient mouse model and in vitro investigations.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results\u2014<\/jats:title>\n            <jats:p>\n              Homozygous deletion of\n              <jats:italic>Opg<\/jats:italic>\n              in apolipoprotein E\u2013deficient mice (\n              <jats:italic>ApoE<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              <jats:italic>Opg<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              ) inhibited angiotensin II-induced aortic dilatation. Survival free from aortic rupture was increased from 67% in\n              <jats:italic>ApoE<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              <jats:italic>Opg<\/jats:italic>\n              <jats:sup>+\/+<\/jats:sup>\n              controls to 94% in\n              <jats:italic>ApoE<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              <jats:italic>Opg<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice (\n              <jats:italic>P<\/jats:italic>\n              =0.040). Serum concentrations of proinflammatory cytokines\/chemokines, and aortic expression for cathepsin S (CTSS), matrix metalloproteinase 2, and matrix metalloproteinase 9 after 7 days (early-phase) of angiotensin II infusion were significantly reduced in\n              <jats:italic>ApoE<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              <jats:italic>Opg<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice compared with\n              <jats:italic>ApoE<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              <jats:italic>Opg<\/jats:italic>\n              <jats:sup>+\/+<\/jats:sup>\n              controls. In addition, aortic expression of markers for an inflammatory phenotype in aortic vascular smooth muscle cells in response to early-phase of angiotensin II infusion was significantly lower in\n              <jats:italic>Opg<\/jats:italic>\n              -deficient mice. In vitro, human abdominal aortic aneurysm vascular smooth muscle cells produced more CTSS and exhibited increased CTSS-derived elastolytic activity than healthy aortic vascular smooth muscle cells, whereas recombinant human osteoprotegerin stimulated CTSS-dependent elastase activity in aortic vascular smooth muscle cells.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>These findings support a role for osteoprotegerin in aortic aneurysm through upregulation of CTSS, matrix metalloproteinase 2, and matrix metalloproteinase 9 within the aorta, promoting an inflammatory phenotype in aortic vascular smooth muscle cells in response to angiotensin II.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.114.304587","type":"journal-article","created":{"date-parts":[[2014,10,10]],"date-time":"2014-10-10T03:10:04Z","timestamp":1412910604000},"page":"2609-2616","update-policy":"http:\/\/dx.doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":28,"title":["Osteoprotegerin Deficiency Limits Angiotensin II\u2013Induced Aortic Dilatation and Rupture in the Apolipoprotein E\u2013Knockout Mouse"],"prefix":"10.1161","volume":"34","author":[{"given":"Corey S.","family":"Moran","sequence":"first","affiliation":[{"name":"From the Vascular Biology Unit, Queensland Research Centre for Peripheral Vascular Disease, School of Medicine and Dentistry, James Cook University, Townsville, Queensland, Australia (C.S.M., R.J.J., E.B., J.G.); and Department of Vascular and Endovascular Surgery, The Townsville Hospital, Townsville, Queensland, Australia (J.G.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roby J.","family":"Jose","sequence":"additional","affiliation":[{"name":"From the Vascular Biology Unit, Queensland Research Centre for Peripheral Vascular Disease, School of Medicine and Dentistry, James Cook University, Townsville, Queensland, Australia (C.S.M., R.J.J., E.B., J.G.); and Department of Vascular and Endovascular Surgery, The Townsville Hospital, Townsville, Queensland, Australia (J.G.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erik","family":"Biros","sequence":"additional","affiliation":[{"name":"From the Vascular Biology Unit, Queensland Research Centre for Peripheral Vascular Disease, School of Medicine and Dentistry, James Cook University, Townsville, Queensland, Australia (C.S.M., R.J.J., E.B., J.G.); and Department of Vascular and Endovascular Surgery, The Townsville Hospital, Townsville, Queensland, Australia (J.G.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan","family":"Golledge","sequence":"additional","affiliation":[{"name":"From the Vascular Biology Unit, Queensland Research Centre for Peripheral Vascular Disease, School of Medicine and Dentistry, James Cook University, Townsville, Queensland, Australia (C.S.M., R.J.J., E.B., J.G.); and Department of Vascular and Endovascular Surgery, The Townsville Hospital, Townsville, Queensland, Australia 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