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Cardiomyocyte-specific deletion of the vitamin D receptor gene results in cardiac hypertrophy.

BACKGROUND: 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. METHODS AND RESULTS: 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 T 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. CONCLUSIONS: 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.

Pubmed ID: 21947295


  • Chen S
  • Law CS
  • Grigsby CL
  • Olsen K
  • Hong TT
  • Zhang Y
  • Yeghiazarians Y
  • Gardner DG



Publication Data

October 25, 2011

Associated Grants

  • Agency: NHLBI NIH HHS, Id: HL096047
  • Agency: NHLBI NIH HHS, Id: HL45637
  • Agency: NHLBI NIH HHS, Id: R01 HL045637
  • Agency: NHLBI NIH HHS, Id: R01 HL045637-09
  • Agency: NHLBI NIH HHS, Id: R21 HL096047
  • Agency: NHLBI NIH HHS, Id: R21 HL096047-01A1

Mesh Terms

  • Animals
  • Cardiomegaly
  • Gene Deletion
  • Gene Targeting
  • Mice
  • Mice, 129 Strain
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Myocytes, Cardiac
  • Receptors, Calcitriol