Glycated albumin promotes a generalized vasculopathy in the db/db mouse.
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 vasculopathy in vivo. Plasma concentrations of fibronectin, a sensitive marker of endothelial cell damage, were increased two-fold in diabetic db/db mice compared with their nondiabetic db/m littermates. 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.
Cohen
M P
MP
Department of Medicine and Biochemistry, University of Pennsylvania, Philadelphia 19104, USA.
Clements
R S
RS
Cohen
J A
JA
Shearman
C W
CW
D000375:Aging / Q000502:physiology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics / Q000503:physiopathology*; D003925:Diabetic Angiopathies / Q000503:physiopathology* / Q000517:prevention & control; D005353:Fibronectins / Q000097:blood*; D017127:Glycation End Products, Advanced; D051379:Mice; D008817:Mice, Mutant Strains; D012016:Reference Values; D012709:Serum Albumin / Q000276:immunology / Q000633:toxicity*; D000093423:Glycated Serum Albumin
D000911:Antibodies, Monoclonal; D015415:Biomarkers; D001786:Blood Glucose; D005353:Fibronectins; D017127:Glycation End Products, Advanced; D012709:Serum Albumin; D000093423:Glycated Serum Albumin