GLYCATED ALBUMIN PROMOTES A GENERALIZED VASCULOPATHY IN THE DB DB MOUSE/

Increased protein glycation has been mechanistically linked to acceler ated vascular pathobiology in diabetes. Because glycated albumin induc es biosynthetic abnormalities in cultured aortic endothelial cells tha t resemble those associated with macrovascular disease, we sought evid ence that increased glycated albumin is operative in the genesis of di abetic vasculopathy in vivo. Plasma concentrations of fibronectin, a s ensitive marker of endothelial cell damage, were increased two-fold in diabetic db/db mice compared with their nondiabetic dbh littermates. Treatment with monoclonal antibodies specifically reactive with albumi n modified by Amadori glucose adducts normalized fibronectin in diabet ic animals despite persistent hyperglycemia. These findings suggest th at increased glycated albumin causally contributes to diabetic vasculo pathy, and that blocking this influence ameliorates vascular damage. ( C) 1996 Academic Press, Inc.