The calcimimetic calindol prevents high phosphate-induced vascular calcification by upregulating matrix GLA protein

Paola Ciceri, Francesca Elli, Irene Brenna, Elisa Volpi, Diego Brancaccio, Mario Cozzolino

Research output: Contribution to journalArticle

Abstract

Background: High serum phosphate (Pi) levels represent a major issue in dialysis patients, because associate with secondary hyperparathyroidism, vascular calcification (VC), and cardiovascular outcomes. In this population, calcimimetics are used to control secondary hyperparathyroidism, hyperphosphatemia, and, more recently, to delay the progression of VC. The aim of this in vitro study was to investigate the direct effects of the calcimimetic calindol on the progression of high Pi-induced VC. Methods: Rat vascular smooth muscle cells (VSMCs) were incubated with high Pi concentrations, and the effects of calindol were investigated on vascular calcium deposition and VSMC osteoblastic differentiation. Results: Calindol inhibited calcium deposition concentration-dependently with a maximal inhibition of 64.0 ± 5.2% achieved at 100 nM. Furthermore, calindol was able to partially prevent the high Pi-induced bone morphogenic protein 2 (BMP-2) expression upregulation (32.4 ± 4.6% of inhibition; p <0.01). Interestingly, the pretreatment with calindol enhanced the matrix Gla protein (MGP) gene expression significantly, compared to high Pi-treated cells (40.2 ± 6.6% of increase, p <0.01). Conclusions: In conclusion, we demonstrated that the calcimimetic calindol prevents high Pi-induced VC by affecting osteoblastic differentiation in vitro. In particular, the inhibitory effect of calindol on VC is probably due to its stimulatory role on the calcium-sensing receptor, leading to an increase in the synthesis of MGP by VSMCs.

Original languageEnglish
Pages (from-to)75-82
Number of pages8
JournalNephron - Experimental Nephrology
Volume122
Issue number3-4
DOIs
Publication statusPublished - Jun 2013

Keywords

  • Calcimimetic
  • Matrix Gla protein
  • Vascular calcification

ASJC Scopus subject areas

  • Nephrology
  • Physiology
  • Genetics

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