Role of advanced glycation end products (AGEs) and receptor for AGEs (RAGE) in vascular damage in diabetes.
A non-enzymatic reaction between ketones or aldehydes and the amino groups of proteins, lipids and nucleic acids contributes to the aging of macromolecules and to the development and progression of various age-related disorders such as vascular complications of diabetes, Alzheimer's disease, cancer growth and metastasis, insulin resistance and degenerative bone disease. Under hyperglycemic and/or oxidative stress conditions, this process begins with the conversion of reversible Schiff base adducts, and then to more stable, covalently-bound Amadori rearrangement products. Over a course of days to weeks, these early glycation products undergo further reactions and rearrangements to become irreversibly crossed-linked, fluorescent protein derivatives termed advanced glycation end products (AGEs). There is a growing body of evidence that AGE and their receptor RAGE (receptor for AGEs) interaction elicits oxidative stress, inflammatory reactions and thrombosis, thereby being involved in vascular aging and damage. These observations suggest that the AGE-RAGE system is a novel therapeutic target for preventing diabetic vascular complications. In this paper, we review the pathophysiological role of the AGE-RAGE-oxidative stress system and its therapeutic intervention in vascular damage in diabetes. We also discuss here the potential utility of the restriction of food-derived AGEs in diabetic vascular complications.
Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume, Japan. shoichi@med.kurume-u.ac.jp
Sho-ichi
S
Yamagishi
D000375:Aging / Q000378:metabolism; D000818:Animals; D002318:Cardiovascular Diseases / Q000209:etiology / Q000378:metabolism; D003925:Diabetic Angiopathies / Q000209:etiology* / Q000378:metabolism*; D003928:Diabetic Nephropathies / Q000209:etiology / Q000378:metabolism; D003930:Diabetic Retinopathy / Q000209:etiology / Q000378:metabolism; D005502:Food / Q000009:adverse effects; D005504:Food Analysis; D017127:Glycation End Products, Advanced / Q000009:adverse effects / Q000378:metabolism*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000209:etiology / Q000378:metabolism; D008954:Models, Biological; D018384:Oxidative Stress; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism*; D015398:Signal Transduction
D017127:Glycation End Products, Advanced; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic