RAGE: a novel target for drug intervention in diabetic vascular disease.
At high levels as seen in diabetes, glucose reacts with and forms adducts (advanced glycation end products; AGEs) on macromolecules including proteins and DNA, eliciting cellular dysfunction and leading to vascular disease. The major means is through cellular receptors; the best characterized is the receptor for advanced glycation end products (RAGE). Accumulation of both AGE/RAGE in addition to other identified ligands of RAGE, including S100/calgranulins, is the hallmark of this receptor in disease pathogenesis. Blockade of ligand-receptor interaction directly at the protein level, or transgenetically, prevents development of micro vascular (nephropathy) and macro vascular (atherosclerosis/restenosis) disease in small animal models. Furthermore, allelic variants of RAGE exist that alter the protein function and gene expression, which may further affect disease outcome. In conclusion, RAGE is a target for drug development to prevent vascular disease in diabetic and nondiabetic subjects.
Hudson
Barry I
BI
College of Physicians and Surgeons, Columbia University, New York, New York, USA. bh2021@columbia.edu
Schmidt
Ann Marie
AM
D000818:Animals; D003925:Diabetic Angiopathies / Q000378:metabolism* / Q000517:prevention & control; D003928:Diabetic Nephropathies / Q000378:metabolism / Q000517:prevention & control; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D011110:Polymorphism, Genetic; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
D017127:Glycation End Products, Advanced; D008024:Ligands; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic