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 (LaCl(3)) 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 LaCl(3), compared to gadolinium chloride (GdCl(3)), and found different effects on the modulation of VSMC lineage markers, such as α-actin and SM22α. In fact, only LaCl(3) preserved the expression of both VSMC lineage markers compared to high Pi-treated cells. Interestingly, both LaCl(3) and GdCl(3) 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 LaCl(3) completely prevented the matrix GLA protein mRNA levels and osteonectin protein expression elevations induced by high Pi compared to GdCl(3). Finally, LaCl(3), in contrast to GdCl(3), prevented the high Pi-induced downregulation of Axl, a membrane tyrosine kinase receptor involved in apoptosis. Thus, our results suggest that LaCl(3) prevents VC by preserving VSMC lineage markers and by decreasing high Pi-induced osteoblastic differentiation.
|Titolo:||Lanthanum Prevents High Phosphate-Induced Vascular Calcification by Preserving Vascular Smooth Muscle Lineage Markers|
|Autori interni:||CICERI, PAOLA (Primo)|
ELLI, FRANCESCA (Secondo)
VOLPI, ELISA MARIA
BRANCACCIO, DIEGO (Penultimo)
COZZOLINO, MARIO GENNARO (Ultimo)
|Parole Chiave:||Lanthanum ; vascular calcification ; phosphate ; Gadolinium|
|Settore Scientifico Disciplinare:||Settore MED/14 - Nefrologia|
|Data di pubblicazione:||giu-2013|
|Digital Object Identifier (DOI):||10.1007/s00223-013-9709-7|
|Appare nelle tipologie:||01 - Articolo su periodico|
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