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. 2005 Apr 5;111(13):1666-71.
doi: 10.1161/01.CIR.0000160353.27927.70. Epub 2005 Mar 28.

25-hydroxyvitamin D3-1alpha-hydroxylase is expressed in human vascular smooth muscle cells and is upregulated by parathyroid hormone and estrogenic compounds

Dalia Somjen  1 , Yosef Weisman, Fortune Kohen, Batya Gayer, Rona Limor, Orly Sharon, Niva Jaccard, Esther Knoll, Naftali Stern
Affiliations

25-hydroxyvitamin D3-1alpha-hydroxylase is expressed in human vascular smooth muscle cells and is upregulated by parathyroid hormone and estrogenic compounds

Dalia Somjen et al. Circulation. .

Abstract

Background: 1,25(OH)2 vitamin D3 exerts multiple effects in human vascular smooth muscle cells (VSMCs). We therefore tested the possibility that VSMCs possess an endogenous 25-hydroxyvitamin D3-1alpha-hydroxylase system, the final enzyme in the biosynthetic pathway of 1,25(OH)2D3.

Methods and results: We assessed the expression and activity of 25-hydroxyvitamin D3-1alpha-hydroxylase by real-time polymerase chain reaction and the conversion of 25(OH)D3 into 1,25(OH)2D3. First, 25-hydroxyvitamin D3-1alpha-hydroxylase mRNA was identified in cultured VSMCs by real-time polymerase chain reaction. Second, in cells treated daily (3 days) with parathyroid hormone (66 nmol/L), estradiol-17beta (30 nmol/L), raloxifene (3 micromol/L), and the phytoestrogens genistein (3 micromol/L), biochainin A (3 micromol/L), and 6-carboxy biochainin A (30 nmol/L), 25-hydroxyvitamin D3-1alpha-hydroxylase mRNA increased by 43+/-13%, (P<0.05) 7+/-24% (P=NS), 176+/-28% (P<0.01), 65+/-11% (P<0.05), 152+/-24% (P<0.01), and 71+/-9% (P<0.05), respectively. Third, production of 1,25(OH)2D3 from 25(OH)D3 was seen with a Km of 25 ng/mL and increased dose dependently after treatment with parathyroid hormone, genistein, and the phytosetrogen derivative 6-carboxy biochainin A. Estradiol-17beta and biochainin A also increased the generation of 1,25(OH)2D3 by 40+/-23% (P<0.05) and 55+/-13% (P<0.05), respectively.

Conclusions: We provide here the first evidence for the expression of an enzymatically active 25(OH)D3-1alpha-hydroxylase system in human VSMCs, which can be upregulated by parathyroid hormone and estrogenic compounds. Because exogenous vitamin D inhibits VSMC proliferation, the role of this system as an autocrine mechanism to curb changes in VSMC proliferation and phenotype is a subject for future investigation.

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Comment in

  • A new "sunshine" in the vasculature?
    Bachschmid MM, van der Loo B. Bachschmid MM, et al. Circulation. 2005 Apr 5;111(13):1571-3. doi: 10.1161/01.CIR.0000161830.45399.F6. Circulation. 2005. PMID: 15811866 No abstract available.

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