Lanthanum prevents high phosphate-induced vascular calcification by preserving vascular smooth muscle lineage markers

Paola Ciceri, Francesca Elli, Irene Brenna, Elisa Volpi, Solange Romagnoli, Delfina Tosi, Paola Braidotti, Diego Brancaccio, Mario Cozzolino

Research output: Contribution to journalArticle

Abstract

Vascular calcification (VC) represents a major cardiovascular risk factor in chronic kidney disease patients. High phosphate (Pi) levels are strongly associated with VC in this population. Therefore, Pi binders are commonly used to control high Pi levels. The aim of this work was to study the mechanism of action of lanthanum chloride (LaCl3) on the progression of Pi-induced VC through its direct effect on vascular smooth muscle cells (VSMCs) in vitro. High Pi induced VSCM Ca deposition. We evaluated the action of LaCl3, compared to gadolinium chloride (GdCl3), and found different effects on the modulation of VSMC lineage markers, such as α-actin and SM22α. In fact, only LaCl3 preserved the expression of both VSMC lineage markers compared to high Pi-treated cells. Interestingly, both LaCl3 and GdCl3 reduced the high Pi-induced elevations of bone morphogenic protein 2 mRNA expression, with no reduction of the high core binding factor-alpha 1 mRNA levels observed in calcified VSMCs. Furthermore, we also found that only LaCl3 completely prevented the matrix GLA protein mRNA levels and osteonectin protein expression elevations induced by high Pi compared to GdCl3. Finally, LaCl3, in contrast to GdCl3, prevented the high Pi-induced downregulation of Axl, a membrane tyrosine kinase receptor involved in apoptosis. Thus, our results suggest that LaCl3 prevents VC by preserving VSMC lineage markers and by decreasing high Pi-induced osteoblastic differentiation.

Original languageEnglish
Pages (from-to)521-530
Number of pages10
JournalCalcified Tissue International
Volume92
Issue number6
DOIs
Publication statusPublished - Jun 2013

Keywords

  • Gadolinium
  • Lanthanum
  • Phosphate
  • Vascular calcification

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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  • Cite this

    Ciceri, P., Elli, F., Brenna, I., Volpi, E., Romagnoli, S., Tosi, D., Braidotti, P., Brancaccio, D., & Cozzolino, M. (2013). Lanthanum prevents high phosphate-induced vascular calcification by preserving vascular smooth muscle lineage markers. Calcified Tissue International, 92(6), 521-530. https://doi.org/10.1007/s00223-013-9709-7