Association of Autoantibodies against M2-Muscarinic Acetylcholine Receptor with Atrial Fibrosis in Atrial Fibrillation Patients

摘要

Objectives. To investigate the association of serum autoantibodies against M2-muscarinic acetylcholine receptor (anti-M2-R) with atrial fibrosis in long-standing persistent atrial fibrillation (AF) patients. Methods. Twenty-four long-standing persistent AF patients, scheduled to undergo hybrid ablation surgery, were enrolled in the study. Twenty-six patients with sinus rhythm, scheduled to undergo coronary artery bypass grafting surgery, were enrolled into the non-AF group. We detected serum anti-M2-R levels. Left atrial appendages were subjected to histological and molecular biological assays. Patients in the AF group received follow-up for two years. Results. The AF group showed significantly higher serum anti-M2-R levels compared to the non-AF group (496.2?±?232.5 vs. 86.3?±?25.7?pmol/L, p0.001). The AF group exhibited severe fibrosis in the left atrial appendages, as indicated by increased collagen volume fraction (45.2?±?4.7% vs. 27.6?±?8.3%, p0.001), and higher levels of collagen I (0.52?±?0.04 vs. 0.24?±?0.06, p0.001) and collagen III (0.51?±?0.07 vs. 0.36?±?0.09, p0.001). TGF-β1 and CTGF were also upregulated in the AF group. A positive correlation between serum anti-M2-R levels and fibrosis of the left atrial appendage and fibrogenic indexes was observed. Conclusions. Serum anti-M2-R levels are higher in AF patients and are associated with the severity of atrial fibrosis. In addition, serum anti-M2-R levels are positively correlated to TGF-β1 and CTGF expression in the left atrial appendage.