RT Journal Article
T1 Extracellular PBEF/NAMPT/visfatin activates pro-inflammatory signalling in human vascular smooth muscle cells through nicotinamide phosphoribosyltransferase activity
A1 Romacho, Tania
A1 Azcutia Criado, Verónica
A1 Vázquez-Bella, Marta
A1 Matesanz, Nuria
A1 Cercas, Elena
A1 Nevado, Julián
A1 Carraro, Raffaele
A1 Rodríguez-Mañas, Leocadio
A1 Sánchez-Ferrer, Carlos Félix
A1 Peiró, Concepción
AB Aims/hypothesisExtracellular pre-B cell colony-enhancing factor/nicotinamide phosphoribosyltransferase/visfatin (ePBEF/NAMPT/visfatin) is an adipocytokine, whose circulating levels are enhanced in metabolic disorders, such as diabetes mellitus and obesity. Here, we explored the ability of ePBEF/NAMPT/visfatin to promote vascular inflammation, as a condition closely related to atherothrombotic diseases. We specifically studied the ability of PBEF/NAMPT/visfatin to directly activate pathways leading to inducible nitric oxide synthase (iNOS) induction in cultured human aortic smooth muscle cells, as well as the mechanisms involved.MethodsiNOS levels and extracellular signal-regulated kinase (ERK) 1/2 activity were determined by western blotting. Nuclear factor (NF)-κB activity was assessed by electrophoretic mobility shift assay.ResultsePBEF/NAMPT/visfatin (10–250 ng/ml) induced iNOS in a concentration-dependent manner. At a submaximal concentration (100 ng/ml), ePBEF/NAMPT/visfatin time-dependently enhanced iNOS levels up to 18 h after stimulation. Over this time period, ePBEF/NAMPT/visfatin elicited a sustained activation of NF-κB and triggered a biphasic ERK 1/2 activation. By using the respective ERK 1/2 and NF-κB inhibitors, PD98059 and pyrrolidine dithiocarbamate, we established that iNOS induction by ePBEF/NAMPT/visfatin required the consecutive upstream activation of ERK 1/2 and NF-κB. The pro-inflammatory action of ePBEF/NAMPT/visfatin was not prevented by insulin receptor blockade. However, exogenous nicotinamide mononucleotide, the product of NAMPT activity, mimicked NF-κB activation and iNOS induction by ePBEF/NAMPT/visfatin, while the NAMPT inhibitor APO866 prevented the effects of ePBEF/NAMPT/visfatin on iNOS and NF-κB.Conclusions/interpretationThrough its intrinsic NAMPT activity, ePBEF/NAMPT/visfatin appears to be a direct contributor to vascular inflammation, a key feature of atherothrombotic diseases linked to metabolic disorders.
PB SpringerNature
SN 0012-186X
YR 2009
FD 2009-08-29
LK https://hdl.handle.net/20.500.14352/101107
UL https://hdl.handle.net/20.500.14352/101107
LA eng
NO Romacho T, Azcutia V, Vázquez-Bella M, Matesanz N, Cercas E, Nevado J, et al. Extracellular PBEF/NAMPT/visfatin activates pro-inflammatory signalling in human vascular smooth muscle cells through nicotinamide phosphoribosyltransferase activity. Diabetologia 2009;52:2455–63. https://doi.org/10.1007/s00125-009-1509-2.
NO Ministerio de Educación y Ciencia (España)
NO Instituto de Salud Carlos III
NO Comunidad de Madrid
NO Fundación de Investigación Médica Mutua Madrileña
NO Instituto Danone
NO Sociedad Española de Farmacología
NO Universidad Autónoma de Madrid
NO Laboratorios Almirall
DS Docta Complutense
RD 21 ene 2026