Bmal1 knockdown in the left stellate ganglion inhibits neural activity and prevents ventricular arrhythmias after myocardial ischemia

Autor: Zhongyang Yu, Zhihao Liu, Liying Jiao, Song Zhang, Liqing Nie, Yueyi Wang, Liping Zhou, Yuhong Wang, Zihan Liu, Xiao Xu, Zeyan Li, Yuyang Zhou, Huixin Zhou, Rui Li, Chen Peng, Lilei Yu, Hong Jiang
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Frontiers in Cardiovascular Medicine, Vol 9 (2022)
Druh dokumentu: article
ISSN: 2297-055X
DOI: 10.3389/fcvm.2022.937608
Popis: ObjectivesThe neural activity of the left stellate ganglion (LSG) is closely related to the occurrence of ventricular arrhythmias (VAs). Bmal1 modulates genes associated with neural activity in the central nervous system. However, few studies indicated the role of Bmal1 in the LSG and the subsequent effect on the heart. Therefore, we aimed to investigate the influence of Bmal1 knockdown in the LSG on its neural activity and cardiac electrophysiology and to explore the mechanisms.Materials and methodsWe used adeno-associated virus (AAV) to knock down Bmal1 in the LSG. Male beagles were randomized into the Bmal1 knockdown group and the control group. After 4 weeks of injection, the LSG function, neural activity, left ventricular effective refractory period (ERP), and action potential duration (APD) were measured. Electrocardiography for 1 h was recorded for VAs analysis after myocardial ischemia. Nerve growth factor (NGF) and c-fos in the LSG were quantified by immunofluorescence. Transcriptomic analysis was performed to assess the gene expression in the LSG.ResultsBmal1 was sufficiently knocked down by AAV. Compared with the control group, heart rate variability (HRV) in the knockdown group was altered. Bmal1 knockdown inhibited neural activity and function of LSG. It also prolonged ERP as well as APD90. Ischemia-induced VAs were significantly reduced. Nerve growth factor (NGF) and c-fos in the LSG were reduced. Bmal1 knockdown led to the expression changes of genes associated with neural activity in the LSG.ConclusionBmal1 knockdown in the LSG suppresses neural activity and prevents ventricular arrhythmias after myocardial ischemia.
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