Anti-M2 muscarinic acetylcholine receptor autoantibodies: New therapeutic targets in atrial fibrillation

Atrial fibrillation is a major and growing public health problem in the world. Heart failure is one of the most common clinical settings for chronic AF. The mechanism underlying AF is still not fully understood. Increasing evidence suggests that activation of G-protein-coupled receptors by autoantibodies may contribute to the pathophysiology of cardiac diseases and stimulatory anti-M2 muscarinic acetylcholine receptor autoantibodies (M2-AABs) were detected in several heart diseases such as dilated cardiomyopathy and Chagas's heart disease. Functional studies have demonstrated that these autoantibodies are able not only to bind to target receptors in the myocardium, but also to induce receptor-mediated biological responses, as partial agonists, which triggers neurotransmitter-receptor-mediated biological effects. Clinical investigation shows that AF was more common in M2-AAB-positive than in M2-AAB-negative patients. Thus, it is a reasonable hypothesis that M2-AABs may participate in the induction and perpetuation of AF. Studies to confirm this hypothesis may lead to new directions in the study of the pathogenesis of AF and the development of a new therapeutic option for this disorder.