[Products of advanced glycosylation and the pathogenesis of accelerated atherosclerosis in diabetes].
The formation of advanced glycosylation end-products (AGEs) is an important biochemical abnormality that accompanies diabetes mellitus. Advanced glycosylation is a process resulting from the spontaneous covalent reaction of circulating glucose with free amino groups of several proteins. Subsequent rearrangement reactions produce fluorescent moieties that remain irreversibly bound to proteins. In this review we summarize and discuss recent studies indicating that effects of AGEs on vascular wall homeostasis may account for the rapidly progressive atherosclerosis associated with diabetes mellitus. Within the vascular wall, collagen-linked AGEs "trap" plasma proteins, quench nitric oxide activity, and interact with specific macrophage receptors to induce cytokine and growth factor release. On plasma low density lipoproteins (LDL), AGEs initiate oxidative reactions that promote the formation of oxidized LDL. Interaction of AGEs with endothelial cells produce an increase in vascular permeability, the expression of procoagulant activity, and the generation of oxidative stress resulting in increased endothelial expression of adhesion molecules for leukocytes. Since early steps of atherosclerosis involve alterations of blood-vessel wall interactions initiating an inflammatory-proliferative process, a better understanding of the biochemical mechanisms by which AGEs contribute to this process, could be relevant to devise preventive and therapeutic strategies for atherosclerosis in diabetes.
Basta
G
G
Istituto di Fisiologia Clinica-C.N.R., Pisa.
De Caterina
R
R
D001161:Arteriosclerosis / Q000209:etiology* / Q000473:pathology; D001778:Blood Coagulation Disorders / Q000209:etiology; D002463:Cell Membrane Permeability; D002477:Cells / Q000378:metabolism; D003925:Diabetic Angiopathies / Q000209:etiology* / Q000473:pathology; D017127:Glycation End Products, Advanced / Q000096:biosynthesis* / Q000737:chemistry; D006801:Humans; D050356:Lipid Metabolism; D010084:Oxidation-Reduction
D017127:Glycation End Products, Advanced