title: Lanthanum prevents high phosphate-induced vascular calcification by preserving vascular smooth muscle lineage markers.
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.
authors: Laboratory of Experimental Nephrology, Dipartimento di Scienze della Salute, Università di Milano, Milan, Italy.
authors: Paola
authors: P
authors: Ciceri
authors: Francesca
authors: F
authors: Elli
authors: Irene
authors: I
authors: Brenna
authors: Elisa
authors: E
authors: Volpi
authors: Solange
authors: S
authors: Romagnoli
authors: Delfina
authors: D
authors: Tosi
authors: Paola
authors: P
authors: Braidotti
authors: Diego
authors: D
authors: Brancaccio
authors: Mario
authors: M
authors: Cozzolino
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002114:Calcinosis / Q000139:chemically induced / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D019070:Cell Lineage; D002478:Cells, Cultured; D005682:Gadolinium / Q000494:pharmacology; D007811:Lanthanum / Q000494:pharmacology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects*; D010710:Phosphates / Q000009:adverse effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D061205:Vascular Calcification / Q000378:metabolism*
chemical_list: D010710:Phosphates; C028521:lanthanum chloride; D007811:Lanthanum; D005682:Gadolinium