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[Advanced glycation end products are involved in microvascular permeability changes observed in microcirculation of
E Bonnardel-Phu1, J L Wautier, E Vicaut
1Laboratoire d'Etude de la Microcirculation, Département de Biophysique, Hôpital F. Widal. 200, rue du Faubourg Saint-Denis, 75475 Paris Cedex 10.
Aim:
Since chronic hyperglycemia leads to Advanced Glycation End Products (AGE) formation, we were interested in its involvement in changes in microvascular permeability during diabetes.
Methods:
Intravital microscopy was used to study changes in microvascular permeability during diabetes. The extravasation of a fluorescent macromolecular tracer (FITC-Albumin) was measured for one hour and, after computer-aided image analysis, was expressed as variations of normalized grey levels (arbitrary units).
Results:
The extravasation of the tracer was increased in diabetic rats. An intravenous bolus of s-RAGE (extracellular domain of the AGE receptor) inhibits dose-dependently this increase (fig. 1). The increase of the extravasation of the macromolecular tracer can be inhibited when s-RAGE are administered 1 and 3 hours before the experiment, but not when administered 1/4 hour and 12 hours before experiment (fig. 2). Administration of antibodies against AGE receptors also inhibits the increase of permeability observed in diabetic rats (fig. 3).
Conclusion:
AGE interaction with their receptor is responsible for an increase in microvascular permeability.