Regular Article
Glycated Albumin Promotes a Generalized Vasculopathy in thedb/dbMouse

https://doi.org/10.1006/bbrc.1996.0014Get rights and content
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Abstract

Increased protein glycation has been mechanistically linked to accelerated vascular pathobiology in diabetes. Because glycated albumin induces biosynthetic abnormalities in cultured aortic endothelial cells that resemble those associated with macrovascular disease, we sought evidence that increased glycated albumin is operative in the genesis of diabetic vasculopathyin vivo. Plasma concentrations of fibronectin, a sensitive marker of endothelial cell damage, were increased two-fold in diabeticdb/dbmice compared with their nondiabeticdb/mlittermates. Treatment with monoclonal antibodies specifically reactive with albumin modified by Amadori glucose adducts normalized fibronectin in diabetic animals despite persistent hyperglycemia. These findings suggest that increased glycated albumin causally contributes to diabetic vasculopathy, and that blocking this influence ameliorates vascular damage.

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