Cadherin‐11 deficiency mitigates high‐fat diet‐induced inflammatory atrial remodeling and vulnerability to atrial fibrillation
- 16 January 2021
- journal article
- research article
- Published by Wiley in Journal of Cellular Physiology
- Vol. 236 (8), 5725-5741
- https://doi.org/10.1002/jcp.30257
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.Funding Information
- National Natural Science Foundation of China (81270259, 81873485, 82000309)
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