AGE–RAGE Stress in the Pathophysiology of Atrial Fibrillation and Its Treatment

Abstract

AbstractAtrial fibrillation (AF) is the most common of cardiac arrhythmias. Mechanisms such as atrial structural remodeling and electrical remodeling have been implicated in the pathogenesis of AF. The data to date suggest that advanced glycation end products (AGEs) and its cell receptor RAGE (receptor for AGE) and soluble receptor (sRAGE) are involved in the pathogenesis of AF. This review focuses on the role of AGE–RAGE axis in the pathogenesis of AF. Interaction of AGE with RAGE generates reactive oxygen species, cytokines, and vascular cell adhesion molecules. sRAGE is a cytoprotective agent. The data show that serum levels of AGE and sRAGE, and expression of RAGE, are elevated in AF patients. Elevated levels of sRAGE did not protect the development of AF. This might be due to greater elevation of AGE than sRAGE. Measurement of AGE–RAGE stress (AGE/sRAGE) would be appropriate as compared with measurement of AGE or RAGE or sRAGE alone in AF patients. AGE and its interaction with RAGE can induce AF through alteration in cellular protein and extracellular matrix. AGE and its interaction with RAGE induce atrial structural and electrical remodeling. The treatment strategy should be directed toward reduction in AGE levels, suppression of RAGE expression, blocking of binding of AGE to RAGE, and elevation of sRAGE and antioxidants. In conclusion, AGE–RAGE axis is involved in the development of AF through atrial structural and electrical remodeling. The treatment modalities for AF should include lowering of AGE, suppression of RAGE, elevation of sRAGE, and use of antioxidants.