{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T06:40:45Z","timestamp":1791268845491,"version":"4.1.0"},"reference-count":74,"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":[[2013,2]]},"abstract":"<jats:sec>\n            <jats:title>Objective\u2014<\/jats:title>\n            <jats:p>\n              Calcific aortic valve disease (CAVD) is a major public health problem with no effective treatment available other than surgery. We previously showed that mature heart valves calcify in response to retinoic acid (RA) treatment through downregulation of the SRY transcription factor\n              <jats:italic>Sox9<\/jats:italic>\n              . In this study, we investigated the effects of excess vitamin A and its metabolite RA on heart valve structure and function in vivo and examined the molecular mechanisms of RA signaling during the calcification process in vitro.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results\u2014<\/jats:title>\n            <jats:p>\n              Using a combination of approaches, we defined calcific aortic valve disease pathogenesis in mice fed 200 IU\/g and 20 IU\/g of retinyl palmitate for 12 months at molecular, cellular, and functional levels. We show that mice fed excess vitamin A develop aortic valve stenosis and leaflet calcification associated with increased expression of osteogenic genes and decreased expression of cartilaginous markers. Using a pharmacological approach, we show that RA-mediated\n              <jats:italic>Sox9<\/jats:italic>\n              repression and calcification is regulated by classical RA signaling and requires both RA and retinoid X receptors.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion\u2014<\/jats:title>\n            <jats:p>Our studies demonstrate that excess vitamin A dietary intake promotes heart valve calcification in vivo. Therefore suggesting that hypervitaminosis A could serve as a new risk factor of calcific aortic valve disease in the human population.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.112.300388","type":"journal-article","created":{"date-parts":[[2012,11,30]],"date-time":"2012-11-30T07:24:39Z","timestamp":1354260279000},"page":"285-293","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":31,"title":["Increased Dietary Intake of Vitamin A Promotes Aortic Valve Calcification In Vivo"],"prefix":"10.1161","volume":"33","author":[{"given":"Danielle J.","family":"Huk","sequence":"first","affiliation":[{"name":"From the Center for Cardiovascular and Pulmonary Research, Columbus, OH (D.J.H., H.L.H., J.L.); The Heart Center, Nationwide Children\u2019s Hospital, Columbus, OH (D.J.H., H.L.H., J.L.); Molecular and Cellular Pharmacology Graduate Program, Leonard M. Miller School of Medicine, Miami, FL (D.J.H.); Graduate School of Biomedical Science, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Tokyo, Japan (H.K.); and Department of Pediatrics, The Ohio State University, Columbus,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harriet L.","family":"Hammond","sequence":"additional","affiliation":[{"name":"From the Center for Cardiovascular and Pulmonary Research, Columbus, OH (D.J.H., H.L.H., J.L.); The Heart Center, Nationwide Children\u2019s Hospital, Columbus, OH (D.J.H., H.L.H., J.L.); Molecular and Cellular Pharmacology Graduate Program, Leonard M. Miller School of Medicine, Miami, FL (D.J.H.); Graduate School of Biomedical Science, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Tokyo, Japan (H.K.); and Department of Pediatrics, The Ohio State University, Columbus,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Kegechika","sequence":"additional","affiliation":[{"name":"From the Center for Cardiovascular and Pulmonary Research, Columbus, OH (D.J.H., H.L.H., J.L.); The Heart Center, Nationwide Children\u2019s Hospital, Columbus, OH (D.J.H., H.L.H., J.L.); Molecular and Cellular Pharmacology Graduate Program, Leonard M. Miller School of Medicine, Miami, FL (D.J.H.); Graduate School of Biomedical Science, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Tokyo, Japan (H.K.); and Department of Pediatrics, The Ohio State University, Columbus,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joy","family":"Lincoln","sequence":"additional","affiliation":[{"name":"From the Center for Cardiovascular and Pulmonary Research, Columbus, OH (D.J.H., H.L.H., J.L.); The Heart Center, Nationwide Children\u2019s Hospital, Columbus, OH (D.J.H., H.L.H., J.L.); Molecular and Cellular Pharmacology Graduate Program, Leonard M. Miller School of Medicine, Miami, FL (D.J.H.); Graduate School of Biomedical Science, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Tokyo, Japan (H.K.); and Department of Pediatrics, The Ohio State University, Columbus,..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.110.006767"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.20799"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2011.12.013"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2007.07.041"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1136\/heart.89.7.801"},{"key":"e_1_3_4_7_2","first-page":"441","article-title":"Insights into the use of biomarkers in calcific aortic valve disease.","volume":"19","author":"Beckmann E","year":"2010","unstructured":"Beckmann E, Grau JB, Sainger R, Poggio P, Ferrari G. 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