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




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Background

Hyperglycemia 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 Findings

In 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.

Conclusions

These 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.



Author: Verónica Azcutia, May Abu-Taha, Tania Romacho, Marta Vázquez-Bella, Nuria Matesanz, Francis W. Luscinskas, Leocadio Rodríguez-

Source: http://plos.srce.hr/



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