{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T18:43:09Z","timestamp":1790707389981,"version":"4.1.0"},"reference-count":48,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"17","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2011,10,25]]},"abstract":"<jats:sec>\n            <jats:title>Background\u2014<\/jats:title>\n            <jats:p>A variety of studies carried out using either human subjects or laboratory animals suggest that vitamin D and its analogues possess important beneficial activity in the cardiovascular system. Using Cre-Lox technology we have selectively deleted the vitamin D receptor (VDR) gene in the cardiac myocyte in an effort to better understand the role of vitamin D in regulating myocyte structure and function.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results\u2014<\/jats:title>\n            <jats:p>\n              Targeted deletion of the exon 4 coding sequence in the VDR gene resulted in an increase in myocyte size and left ventricular weight\/body weight versus controls both at baseline and following a 7-day infusion of isoproterenol. There was no increase in interstitial fibrosis. These knockout mice demonstrated a reduction in end-diastolic and end-systolic volume by echocardiography, activation of the fetal gene program (ie, increased atrial natriuretic peptide and alpha skeletal actin gene expression), and increased expression of modulatory calcineurin inhibitory protein 1 (MCIP1), a direct downstream target of calcineurin\/nuclear factor of activated\n              <jats:italic>T<\/jats:italic>\n              cell signaling. Treatment of neonatal cardiomyocytes with 1,25-dihydroxyvitamin D partially reduced isoproterenol-induced MCIP1 mRNA and protein levels and MCIP1 gene promoter activity.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>Collectively, these studies demonstrate that the vitamin D-VDR signaling system possesses direct, antihypertrophic activity in the heart. This appears to involve, at least in part, suppression of the prohypertrophic calcineurin\/NFAT\/MCIP1 pathway. These studies identify a potential mechanism to account for the reported beneficial effects of vitamin D in the cardiovascular system.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circulationaha.111.032680","type":"journal-article","created":{"date-parts":[[2011,9,27]],"date-time":"2011-09-27T06:27:31Z","timestamp":1317104851000},"page":"1838-1847","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":302,"title":["Cardiomyocyte-Specific Deletion of the Vitamin D Receptor Gene Results in Cardiac Hypertrophy"],"prefix":"10.1161","volume":"124","author":[{"given":"Songcang","family":"Chen","sequence":"first","affiliation":[{"name":"From the Diabetes Center (S.C., C.S.L., C.L.G., K.O.) and Department of Medicine (T.-T.H., Y.Z., Y.Y., D.G.G.), University of California at San Francisco, San Francisco, CA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher S.","family":"Law","sequence":"additional","affiliation":[{"name":"From the Diabetes Center (S.C., C.S.L., C.L.G., K.O.) and Department of Medicine (T.-T.H., Y.Z., Y.Y., D.G.G.), University of California at San Francisco, San Francisco, CA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher L.","family":"Grigsby","sequence":"additional","affiliation":[{"name":"From the Diabetes Center (S.C., C.S.L., C.L.G., K.O.) and Department of Medicine (T.-T.H., Y.Z., Y.Y., D.G.G.), University of California at San Francisco, San Francisco, CA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith","family":"Olsen","sequence":"additional","affiliation":[{"name":"From the Diabetes Center (S.C., C.S.L., C.L.G., K.O.) and Department of Medicine (T.-T.H., Y.Z., Y.Y., D.G.G.), University of California at San Francisco, San Francisco, CA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting-Ting","family":"Hong","sequence":"additional","affiliation":[{"name":"From the Diabetes Center (S.C., C.S.L., C.L.G., K.O.) and Department of Medicine (T.-T.H., Y.Z., Y.Y., D.G.G.), University of California at San Francisco, San Francisco, CA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhang","sequence":"additional","affiliation":[{"name":"From the Diabetes Center (S.C., C.S.L., C.L.G., K.O.) and Department of Medicine (T.-T.H., Y.Z., Y.Y., D.G.G.), University of California at San Francisco, San Francisco, CA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yerem","family":"Yeghiazarians","sequence":"additional","affiliation":[{"name":"From the Diabetes Center (S.C., C.S.L., C.L.G., K.O.) and Department of Medicine (T.-T.H., Y.Z., Y.Y., D.G.G.), University of California at San Francisco, San Francisco, CA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David G.","family":"Gardner","sequence":"additional","affiliation":[{"name":"From the Diabetes Center (S.C., C.S.L., C.L.G., K.O.) and Department of Medicine (T.-T.H., Y.Z., Y.Y., D.G.G.), University of California at San Francisco, San Francisco, CA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra070553"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1753-4887.2008.00093.x"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.30.2.150"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/hypertensionaha.108.117630"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/hypertensionaha.107.087288"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrcardio.2009.135"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/79.5.820"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.28.5.1228"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.24.8.1496"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2007-0298"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1525-1497.2002.11033.x"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2008-0784"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(02)02624-4"},{"key":"e_1_3_4_15_2","first-page":"1633","article-title":"Effects of a short-term vitamin D(3) and calcium supplementation on blood pressure and parathyroid hormone levels in elderly women","volume":"86","author":"Pfeifer M","year":"2001","unstructured":"Pfeifer M, Begerow B, Minne HW, Nachtigall D, Hansen C. 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