{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T18:44:29Z","timestamp":1791917069348,"version":"4.3.4"},"reference-count":27,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","license":[{"start":{"date-parts":[[2022,8,1]],"date-time":"2022-08-01T00:00:00Z","timestamp":1659312000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>Patients with thoracic aortopathy are at increased risk of catastrophic aortic dissection, carrying with it substantial mortality and morbidity. Although granular medial calcinosis (medial microcalcification) has been associated with thoracic aortopathy, its relationship to disease severity has yet to be established.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>One hundred one thoracic aortic specimens were collected from 57 patients with thoracic aortopathy and 18 control subjects. Standardized histopathologic scores, immunohistochemistry, and nanoindentation (tissue elastic modulus) were compared with the extent of microcalcification on von Kossa histology and 18F-sodium fluoride autoradiography.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>\n              Microcalcification content was higher in thoracic aortopathy samples with mild (n=28; 6.17 [2.71\u201310.39];\n              <jats:italic>P<\/jats:italic>\n              \u22640.00010) or moderate histopathologic degeneration (n=30; 3.74 [0.87\u201311.80];\n              <jats:italic>P<\/jats:italic>\n              &lt;0.042) compared with control samples (n=18; 0.79 [0.36\u20131.90]). Alkaline phosphatase (n=26;\n              <jats:italic>P<\/jats:italic>\n              =0.0019) and OPN (osteopontin; n=26;\n              <jats:italic>P<\/jats:italic>\n              =0.0045) staining were increased in tissue with early aortopathy. Increasingly severe histopathologic degeneration was related to reduced microcalcification (n=82; Spearman \u03c1, \u22120.51;\n              <jats:italic>P<\/jats:italic>\n              &lt;0.0001)\u2014a process closely linked with elastin loss (n=82; Spearman \u03c1, \u22120.43;\n              <jats:italic>P<\/jats:italic>\n              &lt;0.0001) and lower tissue elastic modulus (n=28; Spearman \u03c1, 0.43;\n              <jats:italic>P<\/jats:italic>\n              =0.026).\n              <jats:sup>18<\/jats:sup>\n              F-sodium fluoride autoradiography demonstrated good correlation with histologically quantified microcalcification (n=66; r=0.76;\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001) and identified areas of focal weakness in vivo.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>\n              Medial microcalcification is a marker of aortopathy, although progression to severe aortopathy is associated with loss of both elastin fibers and microcalcification.\n              <jats:sup>18<\/jats:sup>\n              F-sodium fluoride positron emission tomography quantifies medial microcalcification and is a feasible noninvasive imaging modality for identifying aortic wall disruption with major translational promise.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.122.317111","type":"journal-article","created":{"date-parts":[[2022,6,30]],"date-time":"2022-06-30T09:00:19Z","timestamp":1656579619000},"page":"1048-1059","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":18,"title":["Microcalcification and Thoracic Aortopathy: A Window Into Disease Severity"],"prefix":"10.1161","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9984-8391","authenticated-orcid":true,"given":"Alexander J.","family":"Fletcher","sequence":"first","affiliation":[{"name":"British Heart Foundation Centre for Cardiovascular Science (A.J.F., J.N., M.B.J.S., N.W., D.E.N.), University of Edinburgh, United Kingdom."},{"name":"Department of Child Health, University of Glasgow, School of Medicine and Dentistry, United Kingdom (A.J.F.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7523-1127","authenticated-orcid":true,"given":"Jennifer","family":"Nash","sequence":"additional","affiliation":[{"name":"British Heart Foundation Centre for Cardiovascular Science (A.J.F., J.N., M.B.J.S., N.W., D.E.N.), University of Edinburgh, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0530-8306","authenticated-orcid":true,"given":"Maaz B.J.","family":"Syed","sequence":"additional","affiliation":[{"name":"British Heart Foundation Centre for Cardiovascular Science (A.J.F., J.N., M.B.J.S., N.W., D.E.N.), University of Edinburgh, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5355-3109","authenticated-orcid":true,"given":"Mark G.","family":"Macaskill","sequence":"additional","affiliation":[{"name":"Edinburgh Imaging Facility, Queens Medical Research Institute (M.G.M., A.A.S.T.), University of Edinburgh, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana A.S.","family":"Tavares","sequence":"additional","affiliation":[{"name":"Edinburgh Imaging Facility, Queens Medical Research Institute (M.G.M., A.A.S.T.), University of Edinburgh, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6676-1097","authenticated-orcid":true,"given":"Niki","family":"Walker","sequence":"additional","affiliation":[{"name":"British Heart Foundation Centre for Cardiovascular Science (A.J.F., J.N., M.B.J.S., N.W., D.E.N.), University of Edinburgh, United Kingdom."},{"name":"Scottish Adult Congenital Cardiology Service, Golden Jubilee National Hospital, Clydebank, Glasgow, United Kingdom (N.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Salcudean","sequence":"additional","affiliation":[{"name":"Department of Radiology, Division of Cardiology, Cardiovascular Translational Lab at the Centre for Heart Lung Innovation, St. Paul\u2019s Hospital and University of British Columbia, Vancouver, Canada (H.S., J.A.L., S.L.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathon A.","family":"Leipsic","sequence":"additional","affiliation":[{"name":"Department of Radiology, Division of Cardiology, Cardiovascular Translational Lab at the Centre for Heart Lung Innovation, St. Paul\u2019s Hospital and University of British Columbia, Vancouver, Canada (H.S., J.A.L., S.L.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelvin H.H.","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery, Royal Infirmary of Edinburgh, United Kingdom (K.H.H.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jillian","family":"Madine","sequence":"additional","affiliation":[{"name":"Institute of Systems, Molecular and Integrative Biology, Faculty of Health and Life Sciences (J.M., M.F., R.A.), University of Liverpool, United Kingdom."},{"name":"Liverpool Centre for Cardiovascular Sciences (J.M.), University of Liverpool, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4752-7956","authenticated-orcid":true,"given":"William","family":"Wallace","sequence":"additional","affiliation":[{"name":"Division of Pathology (W.W.), University of Edinburgh, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Field","sequence":"additional","affiliation":[{"name":"Institute of Systems, Molecular and Integrative Biology, Faculty of Health and Life Sciences (J.M., M.F., R.A.), University of Liverpool, United Kingdom."},{"name":"Department of Cardiothoracic Surgery, Liverpool Heart and Chest Hospital (LCCS), United Kingdom (M.F.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7971-4628","authenticated-orcid":true,"given":"David E.","family":"Newby","sequence":"additional","affiliation":[{"name":"British Heart Foundation Centre for Cardiovascular Science (A.J.F., J.N., M.B.J.S., N.W., D.E.N.), University of Edinburgh, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rihab","family":"Bouchareb","sequence":"additional","affiliation":[{"name":"Department of Medicine, Cardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, NY 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