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

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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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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.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.source PLoS ONE Vol. 5 Issue 4 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 info:eu-repo/semantics/article es_ES
dc.identifier.doi 10.1371/journal.pone.0010091 es_ES
dc.identifier.idgrec 061684 es_ES

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