{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T20:16:54Z","timestamp":1790713014976,"version":"4.1.0"},"reference-count":56,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2022,4,19]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">The biological mechanism of action for osteoprotegerin, a soluble decoy receptor for the receptor activator of nuclear factor\u2010kappa B ligand in the vascular structure, has not been elucidated. The study aim was to determine if osteoprotegerin affects aortic structural integrity in angiotensin II (Ang II)\u2010induced hypertension.<\/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              Mortality was higher (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.0001 by log\u2010rank test) in 8\u2010week\u2010old male homozygotes of osteoprotegerin gene\u2010knockout mice given subcutaneous administration of Ang II for 28\u00a0days, with an incidence of 21% fatal aortic rupture and 23% aortic dissection, than in age\u2010matched wild\u2010type mice. Ang II\u2010infused aorta of wild\u2010type mice showed that osteoprotegerin immunoreactivity was present with proteoglycan. The absence of osteoprotegerin was associated with decreased medial and adventitial thickness and increased numbers of elastin breaks as well as with increased periostin expression and soluble receptor activator of nuclear factor\u2010kappa B ligand concentrations. PEGylated human recombinant osteoprotegerin administration decreased all\u2010cause mortality (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001 by log\u2010rank test), the incidence of fatal aortic rupture (\n              <jats:italic>P<\/jats:italic>\n              =0.08), and aortic dissection (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001) with decreasing numbers of elastin breaks, periostin expressions, and soluble receptor activator of nuclear factor\u2010kappa B ligand concentrations in Ang II\u2010infused osteoprotegerin gene\u2010knockout mice.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">These data suggest that osteoprotegerin protects against aortic rupture and dissection in Ang II\u2010induced hypertension by inhibiting receptor activator of nuclear factor\u2010kappa B ligand activity and periostin expression.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.122.025336","type":"journal-article","created":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T09:53:22Z","timestamp":1649757202000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":16,"title":["Angiotensin II Induces Aortic Rupture and Dissection in Osteoprotegerin\u2010Deficient Mice"],"prefix":"10.1161","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9130-109X","authenticated-orcid":false,"given":"Toshihiro","family":"Tsuruda","sequence":"first","affiliation":[{"name":"Division of Internal Medicine, Cardiovascular Medicine and Nephrology Faculty of Medicine University of Miyazaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5487-7594","authenticated-orcid":false,"given":"Atsushi","family":"Yamashita","sequence":"additional","affiliation":[{"name":"Department of Pathology Faculty of Medicine University of Miyazaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Misa","family":"Otsu","sequence":"additional","affiliation":[{"name":"Division of Internal Medicine, Cardiovascular Medicine and Nephrology Faculty of Medicine University of Miyazaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6511-9999","authenticated-orcid":false,"given":"Masanori","family":"Koide","sequence":"additional","affiliation":[{"name":"Institute for Oral Science Matsumoto Dental University Nagano Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9887-9903","authenticated-orcid":false,"given":"Yuko","family":"Nakamichi","sequence":"additional","affiliation":[{"name":"Institute for Oral Science Matsumoto Dental University Nagano Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7260-0652","authenticated-orcid":false,"given":"Yoko","family":"Sekita\u2010Hatakeyama","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Pathology Nara Medical University Nara Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7729-1836","authenticated-orcid":false,"given":"Kinta","family":"Hatakeyama","sequence":"additional","affiliation":[{"name":"Department of Pathology National Cerebral and Cardiovascular Center Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taro","family":"Funamoto","sequence":"additional","affiliation":[{"name":"Division of Orthopedic Surgery Department of Medicine of Sensory and Motor Organs Faculty of Medicine University of Miyazaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Etsuo","family":"Chosa","sequence":"additional","affiliation":[{"name":"Division of Orthopedic Surgery Department of Medicine of Sensory and Motor Organs Faculty of Medicine University of Miyazaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5105-2159","authenticated-orcid":false,"given":"Yujiro","family":"Asada","sequence":"additional","affiliation":[{"name":"Department of Pathology Faculty of Medicine University of Miyazaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuyuki","family":"Udagawa","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Matsumoto Dental University Nagano Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johji","family":"Kato","sequence":"additional","affiliation":[{"name":"Frontier Science Research Center University of Miyazaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuo","family":"Kitamura","sequence":"additional","affiliation":[{"name":"Frontier Science Research Center University of Miyazaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.4065\/79.2.176"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.114.001513"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.117.031264"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.3400\/avd.ctiia09001"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.2310\/6670.2008.00087"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1159\/000342436"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000126921.29919.51"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cr.7290318"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000137189.22999.3f"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81569-X"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80209-3"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1997.6603"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo.139.3.5837"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.112.301099"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10456-008-9127-z"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-004-1652-8"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa013096"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.3174\/ajnr.A0755"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1001\/archophthalmol.2010.76"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1998.8697"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.2042-7158.2010.01120.x"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000121728.14930.DE"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2009.09.001"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.116.307211"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2012-1928"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.115.06689"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2019.172519"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvw025"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.12.9.1260"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvx128"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvw061"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvy006"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvs.2017.11.091"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.2147\/COPD.S190023"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.4307"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0079753"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.116.06375"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2014.05.014"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2021.708656"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1067\/mva.2000.109743"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-04-1190"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-08-2648"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2004-1895"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M116.751974"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2013.06.001"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2020.01.006"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2013.1717"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0609.2010.01446.x"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI130730"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.109.188185"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1159\/000257339"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2011.05.019"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.114.304587"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0147088"},{"key":"e_1_3_2_56_2","first-page":"41","article-title":"Effects of osteoprotegerin\/TNFRSF11B in two models of abdominal aortic aneurysms","volume":"18","author":"Vorkapic E","year":"2018","unstructured":"Vorkapic E, Kunath A, W\u00e5gs\u00e4ter D. Effects of osteoprotegerin\/TNFRSF11B in two models of abdominal aortic aneurysms. Mol Med Rep. 2018;18:41\u201348. doi: 10.3892\/mmr.2018.8936","journal-title":"Mol Med Rep"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0235553"}],"container-title":["Journal of the American Heart Association"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/JAHA.122.025336","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T11:55:19Z","timestamp":1715601319000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/JAHA.122.025336"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,19]]},"references-count":56,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2022,4,19]]}},"alternative-id":["10.1161\/JAHA.122.025336"],"URL":"https:\/\/doi.org\/10.1161\/jaha.122.025336","relation":{},"ISSN":["2047-9980"],"issn-type":[{"value":"2047-9980","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,19]]},"assertion":[{"value":"2022-01-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-03-16","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-04-12","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e025336"}}