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Inflammation Determines the Pro-Adhesive Properties of High Extracellular D-Glucose in Human Endothelial Cells In Vitro and Rat Microvessels In Vivo

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Inflammation Determines the Pro-Adhesive Properties of High Extracellular D-Glucose in Human Endothelial Cells In Vitro and Rat Microvessels In Vivo

dc.contributor.author	Azcutia, Verónica	es_ES
dc.contributor.author	Abu Taha, May	es_ES
dc.contributor.author	Romacho, Tania	es_ES
dc.contributor.author	Vázquez-Bella, Marta	es_ES
dc.contributor.author	Matesanz, Nuria	es_ES
dc.contributor.author	Luscinskas, Francis W.	es_ES
dc.contributor.author	Rodríguez-Mañas, Leocadio	es_ES
dc.contributor.author	Sanz Ferrando, María Jesús	es_ES
dc.contributor.author	Sánchez-Ferrer, Carlos F.	es_ES
dc.contributor.author	Peiró, Concepción	es_ES
dc.date.accessioned	2015-06-29T10:32:26Z
dc.date.available	2015-06-29T10:32:26Z
dc.date.issued	2010	es_ES
dc.identifier.citation	PLoS ONE Vol. 5 Issue 4	es_ES
dc.identifier.uri	http://hdl.handle.net/10550/44790
dc.description.abstract	BackgroundHyperglycemia is acknowledged as an independent risk factor for developing diabetes-associated atherosclerosis. At present, most therapeutic approaches are targeted at a tight glycemic control in diabetic patients, although this fails to prevent macrovascular complications of the disease. Indeed, it remains highly controversial whether or not the mere elevation of extracellular D-glucose can directly promote vascular inflammation, which favors early pro-atherosclerotic events.Methods and FindingsIn the present work, increasing extracellular D-glucose from 5.5 to 22 mmol/L was neither sufficient to induce intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) expression, analyzed by flow cytometry, nor to promote leukocyte adhesion to human umbilical vein endothelial cells (HUVEC) in vitro, measured by flow chamber assays. Interestingly, the elevation of D-glucose levels potentiated ICAM-1 and VCAM-1 expression and leukocyte adhesion induced by a pro-inflammatory stimulus, such as interleukin (IL)-1β (5 ng/mL). In HUVEC, high D-glucose augmented the activation of extracellular signal-regulated kinase 1/2 (ERK 1/2) and nuclear transcription factor-κB (NF-κB) elicited by IL-1β, measured by Western blot and electromobility shift assay (EMSA), respectively, but had no effect by itself. Both ERK 1/2 and NF-κB were necessary for VCAM-1 expression, but not for ICAM-1 expression. In vivo, leukocyte trafficking was evaluated in the rat mesenteric microcirculation by intravital microscopy. In accordance with the in vitro data, the acute intraperitoneal injection of D-glucose increased leukocyte rolling flux, adhesion and migration, but only when IL-1β was co-administered.ConclusionsThese results indicate that the elevation of extracellular D-glucose levels is not sufficient to promote vascular inflammation, and they highlight the pivotal role of a pro-inflammatory environment in diabetes, as a critical factor conditioning the early pro-atherosclerotic actions of hyperglycemia.	es_ES
dc.title	Inflammation Determines the Pro-Adhesive Properties of High Extracellular D-Glucose in Human Endothelial Cells In Vitro and Rat Microvessels In Vivo	es_ES
dc.type	journal article	es_ES
dc.identifier.doi	10.1371/journal.pone.0010091	es_ES
dc.identifier.idgrec	061684	es_ES