Receptor for advanced glycation end-products (RAGE) and soluble RAGE (sRAGE): cardiovascular implications.
Disorders of glucose metabolism are associated with increased risk for cardiovascular disease (CVD) complications, including coronary, peripheral and cerebral arterial disease, that account for the majority of morbidity and mortality among patients with diabetes mellitus (DM). These associations between glucose and CVD risk extend continuously well below the glycaemic thresholds established for the diagnosis of diabetes, including significantly increased risk associated with impaired fasting glucose, impaired glucose tolerance, and even high normal glucose concentrations. While these epidemiological observations have established a clear association between cardiovascular disease and dysglycaemia and suggest a direct causal link, the mechanisms by which hyperglycaemia may contribute to the development, progression and instability of atherosclerosis remain unclear. A number of recent advances in the realm of vascular biology have identified several novel, plausible pathways that might link hyperglycaemia with atherosclerosis, individually or in aggregate. Key among them are the interaction between advanced glycation end-products (AGEs) and the receptor for AGEs (RAGE), which exists as a trans-membrane signalling receptor and as a circulating form, soluble RAGE (sRAGE). The purpose of this review is to provide an overview of the present understanding of RAGE and sRAGE, their plausible role linking perturbed glucose metabolism with the development, progression and instability of atherosclerosis, and the potential therapeutic implications of modulation of this biological system.
Lindsey
Jason B
JB
The Donald W Reynolds Cardiovascular Clinical Research Center, Division of Cardiology, University of Texas Southwestern, Medical Center, 5909 Harry Hines Blvd., Dallas, TX 75235-9047, USA.
Cipollone
Francesco
F
Abdullah
Shuaib M
SM
McGuire
Darren K
DK
D000818:Animals; D048909:Diabetes Complications / Q000097:blood / Q000378:metabolism; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000378:metabolism*; D017127:Glycation End Products, Advanced / Q000097:blood*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D023421:Models, Animal; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism*
D017127:Glycation End Products, Advanced; D007004:Hypoglycemic Agents; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic