Proprotein convertase subtilisin kexin type 9 (PCSK9) secreted by cultured smooth muscle cells reduces macrophages LDLR levels
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Data di Pubblicazione:
2012
Citazione:
Proprotein convertase subtilisin kexin type 9 (PCSK9) secreted by cultured smooth muscle cells reduces macrophages LDLR levels / N. Ferri, G. Tibolla, A. Pirillo, F. Cipollone, A. Mezzetti, S. Pacia, A. Corsini, A.L. Catapano. ((Intervento presentato al 80. convegno EAS Congress tenutosi a Milano nel 2012.
Abstract:
Objective: Proprotein convertase subtilisin kexin type 9 (PCSK9) is an important regulator of hepatic
low -density lipoprotein (LDL)-cholesterol levels. Although PCSK9 is mainly of hepatic origin, extrahepatic
tissues significantly contribute to PCSK9 production and, potentially, local regulation of LDL
receptor expression.
Methods and results: In the present study w e show that, among vascular cells, PCSK9 is
expressed in smooth muscle cells (SMCs) but not in endothelial cells, macrophages and monocytes.
PCSK9 w as also detectable in human atherosclerotic plaques. Conditioned media from SMCs
significantly reduced LDLR expression in human macrophage and in the macrophage cell line J774.
Co-culture experiments also demonstrated the influence of SMCs on LDLR expression in J774.
PCSK9 released from SMCs directly regulated LDLR expression in macrophages as demonstrated by
retroviral overexpression or knockdow n of PCSK9 w ith small interfering RNA and by using
recombinant PCSK9. Moreover, the proteolytic activity of PCSK9 w as not required for LDLR
dow nregulation since cultured media containing either the catalytic inactive PCSK9 or PCSK9 WT had
a similar effect on LDLR in J774. Finally, conditioned media from SMCs affected b-VLDL cholesterol
uptake and PCSK9 expression reduced both LDLR and LDL uptake in J774.
Conclusions: Taken together our data indicate that PCSK9 secreted by human SMCs is functionally
active and capable of reducing LDLR expression in macrophages. A possible direct role for this
protein in foam cell formation and atherogenesis is suggested.
Tipologia IRIS:
14 - Intervento a convegno non pubblicato
Keywords:
LDLR ; VLDL ; smooth muscle cells ; macrophages ; PCSK9
Elenco autori:
N. Ferri, G. Tibolla, A. Pirillo, F. Cipollone, A. Mezzetti, S. Pacia, A. Corsini, A.L. Catapano
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