{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T22:04:22Z","timestamp":1792101862665,"version":"4.4.0"},"reference-count":38,"publisher":"American Society for Clinical Investigation","issue":"9","license":[{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"vor","delay-in-days":52,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"U.S. Department of Defense","award":["PR231375"],"award-info":[{"award-number":["PR231375"]}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"crossref","award":["906531,24CDA1258673"],"award-info":[{"award-number":["906531,24CDA1258673"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["AR075867,HL137241,HL149658"],"award-info":[{"award-number":["AR075867,HL137241,HL149658"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"crossref","award":["UL1TR001881"],"award-info":[{"award-number":["UL1TR001881"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,5,1]]},"abstract":"<jats:p>\n                    Pseudoxanthoma Elasticum (PXE) is a rare disease caused by loss of function of the ATP-binding cassette C (ABC) member 6 (\n                    <jats:italic>Abcc6<\/jats:italic>\n                    ) gene and characterized by ectopic calcification of multiple tissues, but the physiological reasons underlying ectopic calcification in PXE remain unclear. In a murine model of\n                    <jats:italic>Abcc6<\/jats:italic>\n                    -deficient PXE in which animals developed robust cardiac calcification after heart injury, we show the critical importance of the liver in mediating ectopic cardiac calcification. Tissue-specific deletion of\n                    <jats:italic>Abcc6<\/jats:italic>\n                    in the liver, but not in the heart, was sufficient to cause post-injury cardiac calcification. Metabolomics and gene expression analysis demonstrated deficiencies in nucleotide metabolism, cellular energetics, and defects in cellular respiration underlying ectopic calcification in PXE. Functional abnormalities in cellular respiration in the injured heart were similar in animals with global or liver-specific\n                    <jats:italic>Abcc6<\/jats:italic>\n                    deficiency, showing that hepatic\n                    <jats:italic>Abcc6<\/jats:italic>\n                    expression regulated cellular respiration in the injured heart. We show that ectopic calcification in PXE was primarily dystrophic and that treatment with clodronate or etidronate, which prevent the growth of calcium hydroxyapatite mineralization, was sufficient to rescue the phenotype of ectopic cardiac calcification in\n                    <jats:italic>Abcc6<\/jats:italic>\n                    -deficient states. Taken together, these observations highlight the role of the liver in regulating target tissue metabolic and mitochondrial function in causing ectopic calcification in\n                    <jats:italic>Abcc6<\/jats:italic>\n                    -deficient states.\n                  <\/jats:p>","DOI":"10.1172\/jci193499","type":"journal-article","created":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T16:00:58Z","timestamp":1773158458000},"source":"Crossref","is-referenced-by-count":1,"title":["The liver regulates ectopic calcification in Abcc6-deficient models of pseudoxanthoma elasticum"],"prefix":"10.1172","volume":"136","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2681-0138","authenticated-orcid":true,"given":"Yijie","family":"Wang","sequence":"first","affiliation":[{"name":"Division of Cardiology, Department of Medicine, David Geffen School of Medicine,"},{"name":"UCLA Cardiovascular Theme, David Geffen School of Medicine,"},{"name":"Department of Molecular, Cell and Developmental Biology,"},{"name":"Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research,"},{"name":"Molecular Biology Institute,"},{"name":"California Nanosystems Institute,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baiming","family":"Sun","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, David Geffen School of Medicine,"},{"name":"UCLA Cardiovascular Theme, David Geffen School of Medicine,"},{"name":"Department of Molecular, Cell and Developmental Biology,"},{"name":"Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research,"},{"name":"Molecular Biology Institute,"},{"name":"California Nanosystems Institute,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6260-0787","authenticated-orcid":true,"given":"Feiyang","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Molecular, Cell and Developmental Biology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Tao","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, David Geffen School of Medicine,"},{"name":"UCLA Cardiovascular Theme, David Geffen School of Medicine,"},{"name":"Department of Molecular, Cell and Developmental Biology,"},{"name":"Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research,"},{"name":"Molecular Biology Institute,"},{"name":"California Nanosystems Institute,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiqian","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Molecular, Cell and Developmental Biology,"},{"name":"Bioinformatics Interdepartmental Program,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiqiang","family":"Zhou","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, David Geffen School of Medicine,"},{"name":"Department of Microbiology, Immunology and Molecular Genetics,"},{"name":"Department of Human Genetics, David Geffen School of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, David Geffen School of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linlin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, David Geffen School of Medicine,"},{"name":"UCLA Cardiovascular Theme, David Geffen School of Medicine,"},{"name":"Department of Molecular, Cell and Developmental Biology,"},{"name":"Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research,"},{"name":"Molecular Biology Institute,"},{"name":"California Nanosystems Institute,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihao","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, David Geffen School of Medicine,"},{"name":"UCLA Cardiovascular Theme, David Geffen School of Medicine,"},{"name":"Department of Molecular, Cell and Developmental Biology,"},{"name":"Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research,"},{"name":"Molecular Biology Institute,"},{"name":"California Nanosystems Institute,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna","family":"ten Hoeve","sequence":"additional","affiliation":[{"name":"California Nanosystems Institute,"},{"name":"UCLA Metabolomics Center,"},{"name":"Crump Institute of Molecular Imaging,"},{"name":"Department of Molecular and Medical Pharmacology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linsey","family":"Stiles","sequence":"additional","affiliation":[{"name":"Department of Molecular and Medical Pharmacology,"},{"name":"Department of Medicine, Endocrinology, David Geffen School of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Fernandez del Rio","sequence":"additional","affiliation":[{"name":"Department of Medicine, Endocrinology, David Geffen School of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Calvin","family":"Pan","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, David Geffen School of Medicine,"},{"name":"Department of Microbiology, Immunology and Molecular Genetics,"},{"name":"Department of Human Genetics, David Geffen School of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8466-3431","authenticated-orcid":true,"given":"Orian","family":"Shirihai","sequence":"additional","affiliation":[{"name":"Department of Molecular and Medical Pharmacology,"},{"name":"Department of Medicine, Endocrinology, David Geffen School of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shili","family":"Xu","sequence":"additional","affiliation":[{"name":"Crump Institute of Molecular Imaging,"},{"name":"Department of Molecular and Medical Pharmacology,"},{"name":"Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8574-9181","authenticated-orcid":true,"given":"Thomas G.","family":"Graeber","sequence":"additional","affiliation":[{"name":"California Nanosystems Institute,"},{"name":"UCLA Metabolomics Center,"},{"name":"Crump Institute of Molecular Imaging,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7144-7393","authenticated-orcid":true,"given":"Tamer","family":"Sallam","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, David Geffen School of Medicine,"},{"name":"Molecular Biology Institute,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9355-9564","authenticated-orcid":true,"given":"Matteo","family":"Pellegrini","sequence":"additional","affiliation":[{"name":"Department of Molecular, Cell and Developmental Biology,"},{"name":"Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research,"},{"name":"Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, UCLA, Los Angeles, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9013-0228","authenticated-orcid":true,"given":"Aldons J.","family":"Lusis","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, David Geffen School of Medicine,"},{"name":"UCLA Metabolomics Center,"},{"name":"Crump Institute of Molecular Imaging,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0978-2611","authenticated-orcid":true,"given":"Arjun","family":"Deb","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, David Geffen School of Medicine,"},{"name":"UCLA Cardiovascular Theme, David Geffen School of Medicine,"},{"name":"Department of Molecular, Cell and Developmental Biology,"},{"name":"Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research,"},{"name":"Molecular Biology Institute,"},{"name":"California Nanosystems Institute,"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2026,3,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-017-0639-8"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jid.5700115"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/76109"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/76102"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2013.06.003"},{"issue":"6","key":"B6","first-page":"298","article-title":"Cardiovascular manifestations of Pseudoxanthoma elasticum","volume":"102","author":"Mendelsohn","year":"1978","journal-title":"Arch Pathol Lab Med"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1053\/hupa.2000.0311002"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1111\/j.1556-4029.2010.01647.x"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2024.101274"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18091941"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00010.2006"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2012.460"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3390\/jcm12051893"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.4791"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aal1669"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.11.5483"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-005-0071-7"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0607620104"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.4065\/83.9.1032"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000133194.94939.42"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.113.302070"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-02-266296"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1038\/nature22396"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.115.303567"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200522675"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2020.610266"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-022-00619-4"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2013.07.002"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.11.019"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.112.276667"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1093\/dnares\/4.5.351"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2013.09.015"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1126\/science.abn0910"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1038\/s41413-020-0091-6"},{"issue":"4","key":"B35","first-page":"1137","article-title":"Apoptosis and calcification","volume":"9","author":"Kim","year":"1995","journal-title":"Scanning Microsc"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1007\/s00223-009-9271-5"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.111.237420"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1080\/15384101.2015.1024585"}],"container-title":["Journal of Clinical Investigation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.jci.org\/articles\/view\/193499\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T16:34:14Z","timestamp":1779208454000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jci.org\/articles\/view\/193499"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,10]]},"references-count":38,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,3,5]]},"published-print":{"date-parts":[[2026,5,1]]}},"alternative-id":["10.1172\/JCI193499"],"URL":"https:\/\/doi.org\/10.1172\/jci193499","relation":{},"ISSN":["1558-8238"],"issn-type":[{"value":"1558-8238","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,10]]},"article-number":"e193499"}}