title: Vitamin D and Cardiac Differentiation.
abstract: Calcitriol (1,25-dihydroxycholecalciferol or 1,25-D3) is the hormonally active metabolite of vitamin D. Experimental studies of vitamin D receptors and 1,25-D3 establish calcitriol to be a critical regulator of the structure and function of the heart. Clinical studies link vitamin D deficiency with cardiovascular disease (CVD). Emerging evidence demonstrates that calcitriol is highly involved in CVD-related signaling pathways, particularly the Wnt signaling pathway. Addition of 1,25-D3 to cardiomyocyte cells and examination of its effects on cardiomyocytes and mainly Wnt11 signaling allowed the specific characterization of the role of calcitriol in cardiac differentiation. 1,25-D3 is demonstrated to: (i) inhibit cell proliferation without promoting apoptosis; (ii) decrease expression of genes related to the regulation of the cell cycle; (iii) promote formation of cardiomyotubes; (iv) induce expression of casein kinase-1-α1, a negative regulator of the canonical Wnt signaling pathway; and (v) increase expression of noncanonical Wnt11, which has been recognized to induce cardiac differentiation during embryonic development and in adult cells. Thus, it appears that vitamin D promotes cardiac differentiation through negative modulation of the canonical Wnt signaling pathway and upregulation of noncanonical Wnt11 expression. Future work to elucidate the role(s) of vitamin D in cardiovascular disorders will hopefully lead to improvement and potentially prevention of CVD, including abnormal cardiac differentiation in settings such as postinfarction cardiac remodeling.
authors.affiliation: Department of Health & Life Sciences, Charles R. Drew University of Medicine and Science, Los Angeles, California, USA.
authors.forename: Irene M
authors.initials: IM
authors.lastname: Kim
authors.affiliation: Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
authors.forename: Keith C
authors.initials: KC
authors.lastname: Norris
authors.affiliation: Department of Health & Life Sciences, Charles R. Drew University of Medicine and Science, Los Angeles, California, USA; Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA. Electronic address: joartaza@ucla.edu.
authors.forename: Jorge N
authors.initials: JN
authors.lastname: Artaza
mesh_terms: D000818:Animals; D002117:Calcitriol / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology*; D006321:Heart / Q000254:growth & development*; D006801:Humans; D032383:Myocytes, Cardiac / Q000502:physiology*; D014807:Vitamin D / Q000378:metabolism*
chemical_list: D014807:Vitamin D; D002117:Calcitriol
keywords: Calcitriol; Cardiovascular disease; Casein kinase-1-α1; VDR; Wnt11