Decreased connexin 40 expression of the sinoatrial node mediates ischemic stroke-induced arrhythmia in mice.

Autor: Yao ZJ; Department of Anesthesiology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China., Jiang YP; Department of Anesthesiology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China; Department of Anesthesiology, The First Hospital Affiliated to the Army Medical University, Chongqing 400038, China., Yuan D; Department of Anesthesiology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China., Hong P; Department of Anesthesiology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China., He MJ; Department of Anesthesiology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China., Li FX; Department of Anesthesiology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China., Xu SY; Department of Anesthesiology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China., Lin HB; Department of Anesthesiology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China. Electronic address: linhongbin@i.smu.edu.cn., Zhang HF; Department of Anesthesiology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China. Electronic address: zhanghongfei@smu.edu.cn.
Jazyk: angličtina
Zdroj: Experimental neurology [Exp Neurol] 2024 Jun; Vol. 376, pp. 114773. Date of Electronic Publication: 2024 Apr 08.
DOI: 10.1016/j.expneurol.2024.114773
Abstrakt: Background: Arrhythmia is the most common cardiac complication after ischemic stroke. Connexin 40 is the staple component of gap junctions, which influences the propagation of cardiac electrical signals in the sinoatrial node. However, the role of connexin 40 in post-stroke arrhythmia remains unclear.
Methods: In this study, a permanent middle cerebral artery occlusion model was used to simulate the occurrence of an ischemic stroke. Subsequently, an electrocardiogram was utilized to record and assess variations in electrocardiogram measures. In addition, optical tissue clearing and whole-mount immunofluorescence staining were used to confirm the anatomical localization of the sinoatrial node, and the sinoatrial node tissue was collected for RNA sequencing to screen for potential pathological mechanisms. Lastly, the rAAV9-Gja5 virus was injected with ultrasound guidance into the heart to increase Cx40 expression in the sinoatrial node.
Results: We demonstrated that the mice suffering from a permanent middle cerebral artery occlusion displayed significant arrhythmia, including atrial fibrillation, premature ventricular contractions, atrioventricular block, and abnormal electrocardiogram parameters. Of note, we observed a decrease in connexin 40 expression within the sinoatrial node after the ischemic stroke via RNA sequencing and western blot. Furthermore, rAAV9-Gja5 treatment ameliorated the occurrence of arrhythmia following stroke.
Conclusions: In conclusion, decreased connexin 40 expression in the sinoatrial node contributed to the ischemic stroke-induced cardiac arrhythmia. Therefore, enhancing connexin 40 expression holds promise as a potential therapeutic approach for ischemic stroke-induced arrhythmia.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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