RANKL enhances macrophage paracrine pro-calcific activity in high phosphate-treated smooth muscle cells: dependence on IL-6 and TNF-α.
J Vasc Res
; 49(6): 510-21, 2012.
Article
en En
| MEDLINE
| ID: mdl-22948607
ABSTRACT
BACKGROUND:
Vascular calcification is highly correlated with cardiovascular disease (CVD) morbidity and mortality, and it is associated with inflammation. Receptor activator of NF-ĸB ligand (RANKL) inhibition in vivo has been shown to reduce vascular calcification in a mouse model of atherosclerosis. Therefore, we tested the hypothesis that RANKL regulates smooth muscle cell (SMC) calcification by modulating macrophage production of pro-calcific cytokines.METHODS:
We used a bone marrow-derived macrophage (BMDM)/SMC co-culture system and examined the effects of RANKL on BMDM activation and SMC matrix calcification.RESULTS:
Treatment with RANKL alone did not stimulate SMC calcification induced by elevated phosphate. BMDMs differentiated with macrophage colony-stimulating factor and placed in co-culture with SMCs increased phosphate-induced SMC calcification. RANKL added to the BMDM/SMC co-cultures further enhanced SMC calcification. Treatment of BMDMs with RANKL resulted in increased expression of IL-6 and TNF-α. Thus, increased expression of these pro-calcific cytokines in macrophages may mediate RANKL-induced SMC calcification in a paracrine fashion. Addition of neutralizing IL-6 and TNF-α antibodies together with RANKL treatment significantly reduced the RANKL induction of SMC calcification.CONCLUSION:
RANKL activation of pro-inflammatory and pro-calcific pathways in macrophages may contribute to vascular calcification and inflammation.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Fosfatos
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Calcinosis
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Interleucina-6
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Factor de Necrosis Tumoral alfa
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Miocitos del Músculo Liso
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Ligando RANK
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Macrófagos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Año:
2012
Tipo del documento:
Article