<oai_dc:dc xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:oai_dc="http://www.openarchives.org/OAI/2.0/oai_dc/" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xsi:schemaLocation="http://www.openarchives.org/OAI/2.0/oai_dc/ http://www.openarchives.org/OAI/2.0/oai_dc.xsd">
  <dc:title xml:lang="eng">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</dc:title>
  <dc:language>eng</dc:language>
  <dc:format>application/pdf</dc:format>
  <dc:type xml:lang="eng">Text</dc:type>
  <dc:type xml:lang="eng">journal article</dc:type>
  <dc:type xml:lang="ita">Testo</dc:type>
  <dc:type xml:lang="ita">Articolo di rivista</dc:type>
  <dc:creator>Ana Zupcic</dc:creator>
  <dc:creator>Nejla Latic</dc:creator>
  <dc:creator>Mhaned Oubounyt</dc:creator>
  <dc:creator>Alice Ramesova</dc:creator>
  <dc:creator>Geert Carmeliet</dc:creator>
  <dc:creator>Jan Baumbach</dc:creator>
  <dc:creator>Maria L Elkjaer</dc:creator>
  <dc:creator>Reinhold G Erben</dc:creator>
  <dc:subject xml:lang="eng">Vitamin D</dc:subject>
  <dc:subject xml:lang="eng">Vitamin D Receptor</dc:subject>
  <dc:subject xml:lang="eng">Left Ventricular Hypertrophy</dc:subject>
  <dc:subject xml:lang="eng">Cardiomyocytes</dc:subject>
  <dc:subject xml:lang="eng">Spatial Transcriptomics</dc:subject>
  <dc:subject xml:lang="eng">Inflammation</dc:subject>
  <dc:subject xml:lang="eng">Fibrosis</dc:subject>
  <dc:description xml:lang="eng">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.</dc:description>
  <dc:rights>http://creativecommons.org/licenses/by/4.0/</dc:rights>
  <dc:type xml:lang="deu">Text</dc:type>
  <dc:type xml:lang="deu">Wissenschaftlicher Artikel</dc:type>
  <dc:publisher>MDPI</dc:publisher>
  <dc:identifier>doi:10.3390/ijms25115929</dc:identifier>
  <dc:rights xml:lang="eng">© 2024 by the authors</dc:rights>
  <dc:rights xml:lang="eng">open access</dc:rights>
  <dc:source xml:lang="eng">International Journal of Molecular Sciences</dc:source>
  <dc:date>2024</dc:date>
  <dc:identifier>https://phaidra.vetmeduni.ac.at/o:4446</dc:identifier>
</oai_dc:dc>