{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T06:37:58Z","timestamp":1793083078758,"version":"4.5.0"},"reference-count":40,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2021,2]]},"abstract":"<jats:sec>\n            <jats:title>Objective:<\/jats:title>\n            <jats:p>Vascular calcification is a critical pathology associated with increased cardiovascular event risk, but there are no Food and Drug Administration-approved anticalcific therapies. We hypothesized and validated that an unbiased screening approach would identify novel mediators of human vascular calcification.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results:<\/jats:title>\n            <jats:p>\n              We performed an unbiased quantitative proteomics and pathway network analysis that identified increased CROT (carnitine O-octanoyltransferase) in calcifying primary human coronary artery smooth muscle cells (SMCs). Additionally, human carotid artery atherosclerotic plaques contained increased immunoreactive CROT near calcified regions.\n              <jats:italic>CROT<\/jats:italic>\n              siRNA reduced fibrocalcific response in calcifying SMCs. In agreement, histidine 327 to alanine point mutation inactivated human CROT fatty acid metabolism enzymatic activity and suppressed SMC calcification.\n              <jats:italic>CROT<\/jats:italic>\n              siRNA suppressed type 1 collagen secretion, and restored mitochondrial proteome alterations, and suppressed mitochondrial fragmentation in calcifying SMCs. Lipidomics analysis of SMCs incubated with\n              <jats:italic>CROT<\/jats:italic>\n              siRNA revealed increased eicosapentaenoic acid, a vascular calcification inhibitor. CRISPR\/Cas9-mediated\n              <jats:italic>Crot<\/jats:italic>\n              deficiency in LDL (low-density lipoprotein) receptor-deficient mice reduced aortic and carotid artery calcification without altering bone density or liver and plasma cholesterol and triglyceride concentrations.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>CROT is a novel contributing factor in vascular calcification via promoting fatty acid metabolism and mitochondrial dysfunction, as such CROT inhibition has strong potential as an antifibrocalcific therapy.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.120.315007","type":"journal-article","created":{"date-parts":[[2020,12,24]],"date-time":"2020-12-24T10:02:42Z","timestamp":1608804162000},"page":"755-768","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":40,"title":["CROT (Carnitine O-Octanoyltransferase) Is a Novel Contributing Factor in Vascular Calcification via Promoting Fatty Acid Metabolism and Mitochondrial Dysfunction"],"prefix":"10.1161","volume":"41","author":[{"given":"Takehito","family":"Okui","sequence":"first","affiliation":[{"name":"Center for Interdisciplinary Cardiovascular Sciences, Division of Cardiovascular Medicine (T.O., M.I., M.A.R., A.H., S.K.A., S.K., I.A., H.H., A.R., M.A., S.A.S., E.A.), Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaya","family":"Iwashita","sequence":"additional","affiliation":[{"name":"Center for Interdisciplinary Cardiovascular Sciences, Division of Cardiovascular Medicine (T.O., M.I., M.A.R., A.H., S.K.A., S.K., I.A., H.H., A.R., M.A., S.A.S., E.A.), Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maximillian 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