English   español  
Por favor, use este identificador para citar o enlazar a este item: http://hdl.handle.net/10261/124937
Título

HIF-1α and PFKFB3 mediate a tight relationship between proinflammatory activation and anerobic metabolism in atherosclerotic macrophages

AutorTawakol, Ahmed; Mojena, Marina; Pimentel-Santillana, María ; Narula, Jagat; Enríquez, José Antonio; Través, Paqui G.; Fernández-Velasco, María ; Martín-Sanz, Paloma ; Tejedor, Alberto; Boscá, Lisardo
Fecha de publicación2015
EditorAmerican Heart Association
CitaciónArteriosclerosis, Thrombosis, and Vascular Biology 35: 1463-1471 (2015)
Resumen[Objective]: Although it is accepted that macrophage glycolysis is upregulated under hypoxic conditions, it is not known whether this is linked to a similar increase in macrophage proinflammatory activation and whether specific energy demands regulate cell viability in the atheromatous plaque. [Approach and Results]: We studied the interplay between macrophage energy metabolism, polarization, and viability in the context of atherosclerosis. Cultured human and murine macrophages and an in vivo murine model of atherosclerosis were used to evaluate the mechanisms underlying metabolic and inflammatory activity of macrophages in the different atherosclerotic conditions analyzed. We observed that macrophage energetics and inflammatory activation are closely and linearly related, resulting in dynamic calibration of glycolysis to keep pace with inflammatory activity. In addition, we show that macrophage glycolysis and proinflammatory activation mainly depend on hypoxia-inducible factor and on its impact on glucose uptake, and on the expression of hexokinase II and ubiquitous 6-phosphofructo-2-kinase. As a consequence, hypoxia potentiates inflammation and glycolysis mainly via these pathways. Moreover, when macrophages' ability to increase glycolysis through 6-phosphofructo-2-kinase is experimentally attenuated, cell viability is reduced if subjected to proinflammatory or hypoxic conditions, but unaffected under control conditions. In addition to this, granulocyte-macrophage colony-stimulating factor enhances anerobic glycolysis while exerting a mild proinflammatory activation. [Conclusions]: These findings, in human and murine cells and in an animal model, show that hypoxia potentiates macrophage glycolytic flux in concert with a proportional upregulation of proinflammatory activity, in a manner that is dependent on both hypoxia-inducible factor -1α and 6-phosphofructo-2-kinase.
DescripciónPMCID: PMC4441599.-- et al.
Versión del editorhttps://doi.org/10.1161/ATVBAHA.115.305551
URIhttp://hdl.handle.net/10261/124937
DOI10.1161/ATVBAHA.115.305551
Identificadoresdoi: 10.1161/ATVBAHA.115.305551
issn: 1079-5642
e-issn: 1524-4636
Aparece en las colecciones: (IIBM) Artículos
Ficheros en este ítem:
Fichero Descripción Tamaño Formato  
PFKFB3.pdf1,91 MBAdobe PDFVista previa
Visualizar/Abrir
Mostrar el registro completo
 

Artículos relacionados:


NOTA: Los ítems de Digital.CSIC están protegidos por copyright, con todos los derechos reservados, a menos que se indique lo contrario.