A new in vitro model to delay high phosphate-induced vascular calcification progression

Paola Ciceri, Francesca Elli, Laura Cappelletti, Delfina Tosi, Paola Braidotti, Gaetano Bulfamante, Mario Cozzolino

Research output: Contribution to journalArticle

Abstract

An increasing amount of patients affected by advanced chronic kidney disease suffer from vascular calcification (VC) that associates with cardiovascular morbidity and mortality. In this study, we created a new experimental in vitro model, trying to better elucidate high phosphate (Pi)-induced VC pathogenic mechanisms. Rat aortic vascular smooth muscle cells (VSMCs) were challenged for 7–10 days with high Pi with a repeated and short suspensions of high Pi treatment (intermittent suspension, IS) that was able to induce a significant inhibition of high Pi calcification, maximal at 5 h. Interestingly, the delay in calcification is a consequence of either the absence of free Pi or calcium-phosphate crystals being comparable to the total effect obtained during the 5 h-IS. The protective effect of IS was mediated by the reduction of apoptosis as demonstrated by the action of 20 μmol/L Z-VAD-FMK and by the preservation of the pro-survival receptor Axl expression. Furthermore, autophagy, during IS, was potentiated by increasing the autophagic flux, evaluated by LC3IIB western, while treating VSMCs with 1 mmol/L valproic acid did not affect VC. Finally, IS prevented VSMC osteoblastic differentiation by preserving smooth muscle lineage markers expression. Our data support the hypothesis that to delay significantly VC is necessary and sufficient the IS of high Pi challenge. The IS was able to prevent significantly apoptosis, to induce a potentiation in autophagy, and to prevent osteoblastic differentiation by preserving SM lineage markers.

Original languageEnglish
Pages (from-to)197-206
Number of pages10
JournalMolecular and Cellular Biochemistry
Volume410
Issue number1-2
DOIs
Publication statusPublished - Sep 7 2015

Keywords

  • Apoptosis
  • Phosphate
  • Vascular calcification
  • VSMC

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Molecular Biology
  • Cell Biology

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  • Cite this

    Ciceri, P., Elli, F., Cappelletti, L., Tosi, D., Braidotti, P., Bulfamante, G., & Cozzolino, M. (2015). A new in vitro model to delay high phosphate-induced vascular calcification progression. Molecular and Cellular Biochemistry, 410(1-2), 197-206. https://doi.org/10.1007/s11010-015-2552-6