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Original Article| Volume 27, ISSUE 8, P967-975, August 2018

Vitamin D Improves Cardiac Function After Myocardial Infarction Through Modulation of Resident Cardiac Progenitor Cells

  • Author Footnotes
    1 Co-first authorship.
    Thi Y.L. Le
    Footnotes
    1 Co-first authorship.
    Affiliations
    Centre for Heart Research, Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, Australia

    Department of Cardiology, Westmead Hospital, Sydney, NSW, Australia
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  • Author Footnotes
    1 Co-first authorship.
    Masahito Ogawa
    Footnotes
    1 Co-first authorship.
    Affiliations
    Centre for Heart Research, Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, Australia

    Department of Cardiology, Westmead Hospital, Sydney, NSW, Australia

    Victor Chang Cardiac Research Institute, Sydney, NSW, Australia
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  • Eddy Kizana
    Affiliations
    Centre for Heart Research, Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, Australia

    Department of Cardiology, Westmead Hospital, Sydney, NSW, Australia

    Sydney Medical School, The University of Sydney, Sydney, NSW, Australia
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  • Jenny E. Gunton
    Affiliations
    Centre for Diabetes, Obesity and Endocrinology, Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, Australia

    Sydney Medical School, The University of Sydney, Sydney, NSW, Australia
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  • James J.H. Chong
    Correspondence
    Corresponding author at: Department of Cardiology, Level 2, Westmead Hospital, Hawkesbury Road, Westmead, Sydney, NSW, 2145, Australia.
    Affiliations
    Centre for Heart Research, Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, Australia

    Department of Cardiology, Westmead Hospital, Sydney, NSW, Australia

    Sydney Medical School, The University of Sydney, Sydney, NSW, Australia

    Victor Chang Cardiac Research Institute, Sydney, NSW, Australia
    Search for articles by this author
  • Author Footnotes
    1 Co-first authorship.
Published:February 03, 2018DOI:https://doi.org/10.1016/j.hlc.2018.01.006
Vitamin D Improves Cardiac Function After Myocardial Infarction Through Modulation of Resident Cardiac Progenitor Cells
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      Background

      Vitamin D has been implicated in the prevention of heart failure. However the underlying mechanism remains unclear. We hypothesised that these effects may be partially mediated by cardiac stem/progenitor cells (CPCs). Therefore, we examined the effects of 1,25-dihydroxyvitamin D3 (1,25D) on cell cycle activity and differentiation of a previously described CPC population called cardiac colony-forming unit fibroblasts (cCFU-Fs).

      Methods

      cCFU-Fs were isolated from adult male C57Bl/6 mouse hearts using fluorescence-activated cell sorting. The effect of 1,25D on cell proliferation and differentiation were was assessed by colony-forming and fibroblast differentiation assays. Cell cycle was analysed by flow cytometry. Mice with induced myocardial infarction (MI) were treated with 1,25D or vehicle controls and cardiac function assessed by echocardiography.

      Results

      1,25D dose-dependently increased expression of vitamin D receptor (Vdr) and reduced large colony formation. Addition of 1,25D to cCFU-Fs slowed cell proliferation, promoted cell cycle arrest and decreased expression of pro-fibrotic factors during TGF-β-induced fibroblast differentiation of cCFU-Fs. After MI, 1,25D-treated mice had less left ventricular wall thinning and significant improvement in left ventricular systolic function compared to vehicle-treated controls. Although no significant changes in myocardial fibrotic area and cardiomyocyte size were noted, treatment with 1,25D significantly inhibited cardiac interstitial cell proliferation after MI.

      Conclusions

      Vitamin D signalling promotes cardioprotection after myocardial infarction. This may be through modulation of cCFU-F cell cycle. The role of 1,25D and VDR in regulating cardiac stem/progenitor cell function therefore warrants further investigation.

      Keywords

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      Article info

      Publication history

      Published online: February 03, 2018
      Accepted: January 4, 2018
      Received in revised form: December 4, 2017
      Received: September 20, 2017

      Identification

      DOI: https://doi.org/10.1016/j.hlc.2018.01.006

      Copyright

      © 2018 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

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      Linked Article

      • Vitamin D and Cardiovascular Disease
        Heart, Lung and CirculationVol. 27Issue 8
        • Preview
          Vitamin D is a lipid-soluble, steroid hormone that takes two major forms: vitamin D2 (ergocalciferol), found in plants and fortified foods, and vitamin D3 (cholecalciferol), which, in humans, is largely derived from conversion of dehydrocholesterol in the skin, although also acquired from various food sources [1]. Vitamin D3 is converted by 25-hydroxylase in the liver to its inactive metabolite, 25-hydoxyvitamin D3 [25(OH)D], which has a long half-life and is the main measurable form in blood. This, in turn, is converted in the kidneys by 1α-hydoxylase to the bioactive metabolite, 1,25 (OH)2 vitamin D3 [1,25(OH)2D].
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