{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T23:46:47Z","timestamp":1784072807085,"version":"3.55.0"},"reference-count":55,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,5,29]],"date-time":"2024-05-29T00:00:00Z","timestamp":1716940800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Austrian Science Fund","award":["FWF P26534-B13"],"award-info":[{"award-number":["FWF P26534-B13"]}]},{"name":"Austrian Science Fund","award":["031L0309B"],"award-info":[{"award-number":["031L0309B"]}]},{"name":"Austrian Science Fund","award":["R347-2020-2454"],"award-info":[{"award-number":["R347-2020-2454"]}]},{"name":"German Federal Ministry of Education and Research (BMBF)","award":["FWF P26534-B13"],"award-info":[{"award-number":["FWF P26534-B13"]}]},{"name":"German Federal Ministry of Education and Research (BMBF)","award":["031L0309B"],"award-info":[{"award-number":["031L0309B"]}]},{"name":"German Federal Ministry of Education and Research (BMBF)","award":["R347-2020-2454"],"award-info":[{"award-number":["R347-2020-2454"]}]},{"name":"Lundbeckfonden","award":["FWF P26534-B13"],"award-info":[{"award-number":["FWF P26534-B13"]}]},{"name":"Lundbeckfonden","award":["031L0309B"],"award-info":[{"award-number":["031L0309B"]}]},{"name":"Lundbeckfonden","award":["R347-2020-2454"],"award-info":[{"award-number":["R347-2020-2454"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The association between vitamin D deficiency and cardiovascular disease remains a controversial issue. This study aimed to further elucidate the role of vitamin D signaling in the development of left ventricular (LV) hypertrophy and dysfunction. To ablate the vitamin D receptor (VDR) specifically in cardiomyocytes, VDRfl\/fl mice were crossed with Mlcv2-Cre mice. To induce LV hypertrophy experimentally by increasing cardiac afterload, transverse aortic constriction (TAC) was employed. Sham or TAC surgery was performed in 4-month-old, male, wild-type, VDRfl\/fl, Mlcv2-Cre, and cardiomyocyte-specific VDR knockout (VDRCM-KO) mice. As expected, TAC induced profound LV hypertrophy and dysfunction, evidenced by echocardiography, aortic and cardiac catheterization, cardiac histology, and LV expression profiling 4 weeks post-surgery. Sham-operated mice showed no differences between genotypes. However, TAC VDRCM-KO mice, while having comparable cardiomyocyte size and LV fibrosis to TAC VDRfl\/fl controls, exhibited reduced fractional shortening and ejection fraction as measured by echocardiography. Spatial transcriptomics of heart cryosections revealed more pronounced pro-inflammatory and pro-fibrotic gene regulatory networks in the stressed cardiac tissue niches of TAC VDRCM-KO compared to VDRfl\/fl mice. Hence, our study supports the notion that vitamin D signaling in cardiomyocytes plays a protective role in the stressed heart.<\/jats:p>","DOI":"10.3390\/ijms25115929","type":"journal-article","created":{"date-parts":[[2024,5,30]],"date-time":"2024-05-30T10:42:34Z","timestamp":1717065754000},"page":"5929","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Ablation of Vitamin D Signaling in Cardiomyocytes Leads to Functional Impairment and Stimulation of Pro-Inflammatory and Pro-Fibrotic Gene Regulatory Networks in a Left Ventricular Hypertrophy Model in Mice"],"prefix":"10.3390","volume":"25","author":[{"given":"Ana","family":"Zupcic","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, University of Veterinary Medicine, 1210 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5635-5175","authenticated-orcid":false,"given":"Nejla","family":"Latic","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Veterinary Medicine, 1210 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mhaned","family":"Oubounyt","sequence":"additional","affiliation":[{"name":"Institute for Computational Systems Biology, University of Hamburg, Albert-Einstein-Ring 8-10, 22761 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7482-7818","authenticated-orcid":false,"given":"Alice","family":"Ramesova","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Veterinary Medicine, 1210 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geert","family":"Carmeliet","sequence":"additional","affiliation":[{"name":"Department of Chronic Diseases, Metabolism and Ageing, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Baumbach","sequence":"additional","affiliation":[{"name":"Institute for Computational Systems Biology, University of Hamburg, Albert-Einstein-Ring 8-10, 22761 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8596-142X","authenticated-orcid":false,"given":"Maria L.","family":"Elkjaer","sequence":"additional","affiliation":[{"name":"Institute for Computational Systems Biology, University of Hamburg, Albert-Einstein-Ring 8-10, 22761 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0801-6958","authenticated-orcid":false,"given":"Reinhold G.","family":"Erben","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Veterinary Medicine, 1210 Vienna, Austria"},{"name":"Ludwig Boltzmann Institute of Osteology, Heinrich-Collin-Strasse 30, 1140 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2544","DOI":"10.1161\/CIRCULATIONAHA.107.188965","article-title":"Prevention of heart failure: A scientific statement from the American Heart Association Councils on Epidemiology and Prevention, Clinical Cardiology, Cardiovascular Nursing, and High Blood Pressure Research; Quality of Care and Outcomes Research Interdisciplinary Working Group; and Functional Genomics and Translational Biology Interdisciplinary Working Group","volume":"117","author":"Schocken","year":"2008","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"242","DOI":"10.2337\/db09-1011","article-title":"Adiposity, cardiometabolic risk, and vitamin D status: The Framingham Heart Study","volume":"59","author":"Cheng","year":"2010","journal-title":"Diabetes"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1161\/ATVBAHA.108.165886","article-title":"Serum 25-hydroxyvitamin D levels and the prevalence of peripheral arterial disease: Results from NHANES 2001 to 2004","volume":"28","author":"Melamed","year":"2008","journal-title":"Arterioscler. 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