Acute modulation of albumin microvascular leakage by advanced glycation end products in microcirculation of diabetic rats in vivo
Acute modulation of albumin microvascular leakage by advanced glycation end products in microcirculation of diabetic rats in vivo. E Bonnardel-Phu , J L Wautier , A M Schmidt , C Avila and E Vicaut Department of Biophysics, F. Widal Hospital, Paris, France. Abstract Advanced glycation end products (...
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Published in | Diabetes (New York, N.Y.) Vol. 48; no. 10; pp. 2052 - 2058 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
Alexandria, VA
American Diabetes Association
01.10.1999
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Subjects | |
Online Access | Get full text |
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Summary: | Acute modulation of albumin microvascular leakage by advanced glycation end products in microcirculation of diabetic rats
in vivo.
E Bonnardel-Phu ,
J L Wautier ,
A M Schmidt ,
C Avila and
E Vicaut
Department of Biophysics, F. Widal Hospital, Paris, France.
Abstract
Advanced glycation end products (AGEs) are nonenzymatic glycosylated adducts of proteins that accumulate in vascular tissue
during diabetes and aging. The aim of this work was to study the role of AGEs and of the oxidative mechanisms in diabetes-induced
changes in vascular permeability. Intravital videomicroscopy was used to study albumin microvascular leakage in cremaster
muscle. The extravasation of a fluorescent macromolecular tracer (fluorescein isothiocyanate-albumin) was measured for 1 h
and, after computer-aided image analysis, was expressed as variations of normalized gray levels (arbitrary units). Extravasation
of the macromolecular tracer was much higher in diabetic rats than in control rats (slope of extravasation versus time increased
by >100%, P < 10(-4)). This increase was significantly inhibited when we blocked AGEs binding to their endothelial receptor
by intravenous bolus of soluble recombinant receptor to AGEs (rR-RAGE) (slope of extravasation versus time decreased by 19,
30, and 40%, for 0.5, 2.5, and 5.15 mg/kg rR-RAGE, respectively) or by a 6 mg/kg intravenous bolus of antibody against RAGE
(slope decreased by 53%). Systemic injection of probucol (an antioxidant) also significantly inhibited the increase in the
extravasation of the macromolecular tracer occurring in experimental diabetes (slope decreased by 51%, P < 10(-4)). These
results strongly suggest that in experimental diabetes the interaction of circulating AGEs and endothelial RAGE mediates albumin
micro-vascular leakage, possibly via AGE-RAGE-dependent enhanced oxidant stress. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0012-1797 1939-327X |
DOI: | 10.2337/diabetes.48.10.2052 |