Therapeutic Interventions for Advanced Glycation-End Products and its Receptor- Mediated Cardiovascular Disease

Advanced glycation end products (AGEs) are heterogeneous group of molecules formed from nonenzymatic reaction of reducing sugars with amino group of proteins, lipids, and nucleic acid. Interaction of AGEs with its cell-bound receptor (RAGE) results in generation of oxygen radicals, nuclear factor kappa-β, proinflammatory cytokines and cell adhesion molecules, and is involved in the pathophysiology of cardiovascular diseases (CVD). Circulating soluble forms of RAGE (sRAGE) and endo-secretory RAGE (esRAGE) compete with RAGE for ligand binding and function as a decoy. This paper describes the endogenous and exogenous (high dietary AGEs, and cooking food under high dry heat, elevated pH, and longer period) sources of AGEs. AGERAGE- mediated CVD includes atherosclerosis, coronary artery disease, carotid artery disease, hypertension, peripheral vascular diseases, heart failure, cardiomyopathy, and microangiopathy. The therapeutic interventions with reduction in AGEs and RAGE, and elevation in sRAGE has been reported for the treatment of AGE-RAGEmediated CVD. Reduction in levels of AGEs can be achieved by reduction in consumption of food containing low amount of AGEs, cooking food at low temperature, moist heat, and shorter duration. AGE formation can be reduced with drugs, vitamins and stoppage of cigarette smoking. Statins, telmisartan, and curcumin have been used for suppression of RAGE. Statins, ACE-inhibitors, Rosiglitazone and vitamin D have been used to increase levels of sRAGE. Finally exogenous administration of sRAGE can be helpful in amelioration of CVD. In conclusion, AGE-RAGE-mediated CVD could be attenuated with reduction in consumption of AGEs, suppression of RAGE and elevation of sRAGE. Keywords: Advanced glycation end products, receptor for AGE, soluble receptors for AGE, cardiovascular disease, aminoguanidine, statins, dietary AGE, vitamins.