Frontiers in Immunology (Dec 2021)
Interleukin-6-Mediated-Ca2+ Handling Abnormalities Contributes to Atrial Fibrillation in Sterile Pericarditis Rats
- Jie Liao,
- Jie Liao,
- Jie Liao,
- Jie Liao,
- Jie Liao,
- Shaoshao Zhang,
- Shaoshao Zhang,
- Shaoshao Zhang,
- Shaoshao Zhang,
- Shuaitao Yang,
- Shuaitao Yang,
- Shuaitao Yang,
- Shuaitao Yang,
- Yang Lu,
- Yang Lu,
- Yang Lu,
- Yang Lu,
- Kai Lu,
- Kai Lu,
- Kai Lu,
- Kai Lu,
- Yuwei Wu,
- Yuwei Wu,
- Yuwei Wu,
- Yuwei Wu,
- Qiongfeng Wu,
- Qiongfeng Wu,
- Qiongfeng Wu,
- Qiongfeng Wu,
- Ning Zhao,
- Ning Zhao,
- Ning Zhao,
- Ning Zhao,
- Qian Dong,
- Qian Dong,
- Qian Dong,
- Qian Dong,
- Lei Chen,
- Yimei Du,
- Yimei Du,
- Yimei Du,
- Yimei Du
Affiliations
- Jie Liao
- Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Jie Liao
- Research Center of Ion Channelopathy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Jie Liao
- Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Jie Liao
- Key Lab for Biological Targeted Therapy of Education Ministry and Hubei Province, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Jie Liao
- Department of Cardiology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China
- Shaoshao Zhang
- Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Shaoshao Zhang
- Research Center of Ion Channelopathy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Shaoshao Zhang
- Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Shaoshao Zhang
- Key Lab for Biological Targeted Therapy of Education Ministry and Hubei Province, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Shuaitao Yang
- Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Shuaitao Yang
- Research Center of Ion Channelopathy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Shuaitao Yang
- Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Shuaitao Yang
- Key Lab for Biological Targeted Therapy of Education Ministry and Hubei Province, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Yang Lu
- Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Yang Lu
- Research Center of Ion Channelopathy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Yang Lu
- Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Yang Lu
- Key Lab for Biological Targeted Therapy of Education Ministry and Hubei Province, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Kai Lu
- Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Kai Lu
- Research Center of Ion Channelopathy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Kai Lu
- Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Kai Lu
- Key Lab for Biological Targeted Therapy of Education Ministry and Hubei Province, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Yuwei Wu
- Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Yuwei Wu
- Research Center of Ion Channelopathy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Yuwei Wu
- Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Yuwei Wu
- Key Lab for Biological Targeted Therapy of Education Ministry and Hubei Province, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Qiongfeng Wu
- Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Qiongfeng Wu
- Research Center of Ion Channelopathy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Qiongfeng Wu
- Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Qiongfeng Wu
- Key Lab for Biological Targeted Therapy of Education Ministry and Hubei Province, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Ning Zhao
- Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Ning Zhao
- Research Center of Ion Channelopathy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Ning Zhao
- Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Ning Zhao
- Key Lab for Biological Targeted Therapy of Education Ministry and Hubei Province, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Qian Dong
- Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Qian Dong
- Research Center of Ion Channelopathy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Qian Dong
- Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Qian Dong
- Key Lab for Biological Targeted Therapy of Education Ministry and Hubei Province, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Lei Chen
- Department of Physiology, Nanjing Medical University, Nanjing, China
- Yimei Du
- Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Yimei Du
- Research Center of Ion Channelopathy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Yimei Du
- Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Yimei Du
- Key Lab for Biological Targeted Therapy of Education Ministry and Hubei Province, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- DOI
- https://doi.org/10.3389/fimmu.2021.758157
- Journal volume & issue
-
Vol. 12
Abstract
Pre-existing Ca2+ handling abnormalities constitute the arrhythmogenic substrate in patients developing postoperative atrial fibrillation (POAF), a common complication after cardiac surgery. Postoperative interleukin (IL)-6 levels are associated with atrial fibrosis in several animal models of POAF, contributing to atrial arrhythmias. Here, we hypothesize that IL-6-mediated-Ca2+ handling abnormalities contribute to atrial fibrillation (AF) in sterile pericarditis (SP) rats, an animal model of POAF. SP was induced in rats by dusting atria with sterile talcum powder. Anti-rat-IL-6 antibody (16.7 μg/kg) was administered intraperitoneally at 30 min after the recovery of anesthesia. In vivo electrophysiology, ex vivo optical mapping, western blots, and immunohistochemistry were performed to elucidate mechanisms of AF susceptibility. IL-6 neutralization ameliorated atrial inflammation and fibrosis, as well as AF susceptibility in vivo and the frequency of atrial ectopy and AF with a reentrant pattern in SP rats ex vivo. IL-6 neutralization reversed the prolongation and regional heterogeneity of Ca2+ transient duration, relieved alternans, reduced the incidence of discordant alternans, and prevented the reduction and regional heterogeneity of the recovery ratio of Ca2+ transient. In agreement, western blots showed that IL-6 neutralization reversed the reduction in the expression of ryanodine receptor 2 (RyR2) and phosphorylated phospholamban. Acute IL-6 administration to isolated rat hearts recapitulated partial Ca2+ handling phenotype in SP rats. In addition, intraperitoneal IL-6 administration to rats increased AF susceptibility, independent of fibrosis. Our results reveal that IL-6-mediated-Ca2+ handling abnormalities in SP rats, especially RyR2-dysfunction, independent of IL-6-induced-fibrosis, early contribute to the development of POAF by increasing propensity for arrhythmogenic alternans.
Keywords
- Interleukin-6
- postoperative atrial fibrillation
- calcium handling abnormalities
- ryanodine receptor
- alternans
