Abstract: SA-PO855

Direct Inhibition of Phosphate-Induced Vascular Smooth Muscle Cell Calcification via Suppression of PiT2 Expression by 25-Hydroxyvitamin D

Session Information

  • Vascular Calcification
    November 04, 2017 | Location: Hall H, Morial Convention Center
    Abstract Time: 10:00 AM - 10:00 AM

Category: Mineral Disease

  • 1205 Vascular Calcification

Authors

  • Tokumoto, Masanori, Department of Medicine, Fukuoka Dental College, Fukuoka, Japan
  • Yamada, Shunsuke, Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
  • Tsuruya, Kazuhiko, Kyushu University, Fukuoka, Japan
  • Kitazono, Takanari, Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
  • Ooboshi, Hiroaki, Department of Medicine, Fukuoka Dental College, Fukuoka, Japan
Background

Inverse association between 25-hydroxyvitamin D (25(OH)D) level and cardiovascular (CV) risk has been reported. Recently, the low serum 25(OH)D levels, which are frequently recognized in chronic kidney disease, has been also connected with vascular calcification, but the mechanism remains fully unknown. In the present study, we examined whether 25(OH)D directly reduce phosphate (P)-induced vascular smooth muscle cell (VSMC) calcification and its mechanism.

Methods

Human VSMCs were cultured in high P media with the additional P load of 2.0mM to induce calcification and treated with 25(OH)D of 10-10 ~ 10-6 M for a week. The degree of calcification and the expression of intrinsic calcification inhibitors and osteogenic differentiation markers were examined at Day 1 and 7. The degree of calcification was expressed as the calcium (Ca) content precipitated on the human VSMCs, and the content of calciprotein particle (CPP) was expressed as the Ca content in the precipitation of media, centrifuged by 16,000g for 2 hours at room temperature.

Results


Megalin and 1-hydroxylase were expressed in human VSMCs, and P-induced calcification was decreased with 25(OH)D of 10-10 ~ 10-7 M (p<0.01) at Day 7. The PiT1 expression was not altered by administration of 25(OH)D, but the PiT2 expression was decreased with 25(OH)D of 10-10 ~ 10-6 M at Day 1 and 7 (p<0.01). The Ca contents at Day 7 were correlated with the PiT2 expression at Day 1 and 7 (p<0.01, r=0.66 and 0.57, respectively). Furthermore, the CPP content and the SOX9 expression were correlated with the PiT2 expression at Day 1 (p<0.01, r=0.55, and p<0.05, r=0.49, respectively).
Our results indicate that 25(OH)D ameliorates P-induced calcification via the inhibition of PiT2 expression in human VSMCs.

Conclusion

Our results indicate that 25(OH)D ameliorates P-induced calcification via the inhibition of PiT2 expression in human VSMCs.

Funding

  • Government Support - Non-U.S.