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Amadori-modified glycated serum proteins and accelerated atherosclerosis in diabetes: Pathogenic and therapeutic implications

2006; Elsevier BV; Volume: 147; Issue: 5 Linguagem: Inglês

10.1016/j.lab.2005.12.006

1532-6543

Margo P. Cohen, Fuad N. Ziyadeh, Sheldon Chen,

Biochemical effects in animals

Diabetes confers a four-fold risk for atherosclerotic cardiovascular disease, manifest in the vessel wall as intimal thickening, smooth muscle hypertrophy, lipid accumulation, extracellular matrix expansion, and inflammatory cell infiltration. 1 Hansson G.K. Inflammation, atherosclerosis and coronary artery disease. New Engl J Med. 2005; 352: 1685-1695 Google Scholar Although the exact mechanisms responsible for the accelerated atherosclerosis that occurs in patients with diabetes are incompletely defined, evidence is accumulating that Amadori-modified glycated serum proteins may play a substantive role. Numerous studies have indicated that serum proteins containing Amadori glucose adducts, which arise from the nonenzymatic condensation reaction between reducing sugar and susceptible amino groups that is increased in the diabetic state, acquire biologic properties that are strongly linked to the pathogenesis of vascular complications of diabetes. The Amadori modification is structurally distinct from those associated with AGEs, which arise from subsequent oxidation, degradation, and other spontaneous reactions and are implicated in the development of long-term sequelae of diabetes. Additionally, Amadori-modified proteins operate through receptors different from RAGE, the receptors mediating biologic effects of AGE. This review focuses on proatherogenic properties of Amadori-modified serum proteins, which are perhaps underappreciated contributors to atherosclerosis in diabetes. Although the diabetic state promotes the Amadori-modification of many circulating proteins, 2 Jaleel A. Halvatsiotis P. Williamson B. Juhasz P. Martin S. Nair K.S. Identification of Amadori-modified plasma proteins in type 2 diabetes and the effect of short-term intensive insulin treatment. Diabetes Care. 2005; 28: 645-652 Google Scholar giving rise to concentrations of glycated proteins approximately one and a half to three times those found in non-diabetic persons that reflect integrated glycemia to which the protein has been exposed during its residence time in the circulation, information on glycation-induced functional alterations and potential pathophysiologic consequences is most extensive regarding the major plasma constituents albumin and lipoproteins. In the discussion that follows, the terms "glycated albumin" and "glycated lipoprotein," unless otherwise defined, refer to the Amadori constructs.