Advanced glycation end products in diabetes-associated atherosclerosis and renal disease: interventional studies.
There is increasing evidence that advanced glycation end products (AGEs) and their interactions with various receptors (in particular, the receptor RAGE) play a pivotal role in the development and progression of diabetic macro- and microvascular complications. Several approaches have been used to inhibit tissue accumulation of AGEs in diabetes, including inhibitors of AGE formation such as aminoguanidine, ALT 946, and pyridoxamine-or putative cross-link breakers such as ALT 711. Alternative interventions have also included the administration of a soluble receptor for RAGE, sRAGE, thus capturing circulating AGEs and preventing them from binding to the cell-bound full-length receptor RAGE, thereby inhibiting the proinflammatory and profibrotic response following AGE-RAGE binding. In this review we summarize the evidence for such antiglycation therapies in retarding or delaying the development and progression of diabetes-associated atherosclerosis and renal disease while focusing on interventional strategies inhibiting AGE accumulation. In summary, all approaches have been shown to confer some degree of antiatherosclerotic and renoprotective effects, albeit to different degrees and by different mechanisms.
Jandeleit-Dahm
Karin A
KA
Danielle Alberti Memorial Centre for Diabetes Complications, Baker Heart Research Institute, P.O. Box 6492, Melbourne 8008, Australia.
Lassila
Markus
M
Allen
Terri J
TJ
D000577:Amides / Q000627:therapeutic use; D000818:Animals; D001161:Arteriosclerosis / Q000517:prevention & control*; D003925:Diabetic Angiopathies / Q000517:prevention & control*; D003928:Diabetic Nephropathies / Q000517:prevention & control*; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors*; D006801:Humans; D006834:Hydrazines / Q000627:therapeutic use; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors; D013844:Thiazoles / Q000627:therapeutic use
D000577:Amides; D017127:Glycation End Products, Advanced; D006834:Hydrazines; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D013844:Thiazoles; C406794:alagebrium; C468887:ALT-946