The calcimimetic calindol prevents high phosphate-induced vascular calcification by upregulating matrix GLA protein.
Nephron Exp Nephrol
; 122(3-4): 75-82, 2012.
Article
em En
| MEDLINE
| ID: mdl-23548867
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Ligação ao Cálcio
/
Diferenciação Celular
/
Proteínas da Matriz Extracelular
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Calcificação Vascular
/
Indóis
/
Músculo Liso Vascular
/
Naftalenos
Limite:
Animals
Idioma:
En
Revista:
Nephron Exp Nephrol
Assunto da revista:
NEFROLOGIA
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Itália