Abstract
Atrial 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.
Keywords
advanced glycation end products - cell receptor for age - soluble RAGE - atrial fibrillation
- atrial structural remodeling - atrial electrical remodeling - treatment modalities
