Abstract
Atrial fibrillation (AF) is the most common cardiac arrhythmia nowadays. The occurrence of AF is closely associated with obesity. Cadherin-11 (Cad-11), as a member of the cadherin family, can make a contribution to diet-induced obesity and it will be informative to know whether Cad-11 exerts its effects on atrial remodeling and AF vulnerability in a diet-induced obesity model. In this study, we demonstrated that the expression of Cad-11 was significantly upregulated in the left atrium of AF patients with obesity and mice following 16 weeks of high-fat diet (HFD) feeding. Further confirmed that Cad-11 could regulate the activity of atrial fibroblasts by participating in inducing proinflammatory cytokines production. At animal levels, we found that although there was a lack of statistical difference in body weight, Cad-11-/- mice could markedly improve impaired glucose tolerance and hyperlipidemia. Adverse atrial structural remodeling, including atrial enlargement, inflammation, and fibrosis provoked by HFD feeding were mitigated in Cad-11-/- mice. Mechanistically, Cad-11 activated mitogen-activated protein kinases and nuclear factor-κB for interleukin-6 production in atrial fibroblasts that may contribute to the atrial fibrosis process in obesity-related AF, suggesting Cad-11 might be a new therapeutic target for obesity-related AF.