Cardiovascular disease: what's all the AGE/RAGE about?
Advanced glycation end-products (AGEs) are involved in mediating the effects of hyperglycaemia in diabetes. The most important receptor for AGEs is the receptor for advanced glycation end-products (RAGE). Binding of AGEs to RAGE converts transient cellular stimulation into sustained cellular dysfunction driven by long-term activation of the pro-inflammatory transcription factor NF-kB. Different splice variants of RAGE exist, including a soluble form that binds to AGEs but lacks the intracellular domain and thus fails to induce signal transduction. In this context, soluble RAGE may act as a therapeutic agent for AGE-induced effects. The balance between the synthesis of sRAGE and full-length RAGE may be an important determinant of AGE-induced dysfunction. An increasing amount of evidence suggests that AGEs either directly or via their interaction with RAGE play a pivotal role in the development and acceleration of atherosclerotic cardiovascular disease. These effects will be summarised in this review, together with the effects of therapeutic strategies targeting AGE/RAGE interactions. These treatments appear to have significant clinical potential, most likely in combination with currently used agents such as inhibitors of the renin-angiotensin system or statins, to reduce the major burden of diabetes, its associated cardiovascular disease.
Barlovic
Drazenka P
DP
Baker IDI Heart and Diabetes Institute, Melbourne, Australia.
Thomas
Merlin C
MC
Jandeleit-Dahm
Karin
K
D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000378:metabolism*; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000378:metabolism; D016503:Drug Delivery Systems; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism*
D017127:Glycation End Products, Advanced; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic