Frontiers in Cardiovascular Medicine (Sep 2022)

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

  • Zhongyang Yu,
  • Zhongyang Yu,
  • Zhongyang Yu,
  • Zhongyang Yu,
  • Zhongyang Yu,
  • Zhongyang Yu,
  • Zhihao Liu,
  • Zhihao Liu,
  • Zhihao Liu,
  • Zhihao Liu,
  • Zhihao Liu,
  • Zhihao Liu,
  • Liying Jiao,
  • Liying Jiao,
  • Liying Jiao,
  • Liying Jiao,
  • Liying Jiao,
  • Liying Jiao,
  • Song Zhang,
  • Song Zhang,
  • Song Zhang,
  • Song Zhang,
  • Song Zhang,
  • Song Zhang,
  • Liqing Nie,
  • Liqing Nie,
  • Liqing Nie,
  • Liqing Nie,
  • Liqing Nie,
  • Liqing Nie,
  • Yueyi Wang,
  • Yueyi Wang,
  • Yueyi Wang,
  • Yueyi Wang,
  • Yueyi Wang,
  • Yueyi Wang,
  • Liping Zhou,
  • Liping Zhou,
  • Liping Zhou,
  • Liping Zhou,
  • Liping Zhou,
  • Liping Zhou,
  • Yuhong Wang,
  • Yuhong Wang,
  • Yuhong Wang,
  • Yuhong Wang,
  • Yuhong Wang,
  • Yuhong Wang,
  • Zhihao Liu,
  • Zhihao Liu,
  • Zhihao Liu,
  • Zhihao Liu,
  • Zhihao Liu,
  • Zhihao Liu,
  • Zihan Liu,
  • Zihan Liu,
  • Zihan Liu,
  • Zihan Liu,
  • Zihan Liu,
  • Zihan Liu,
  • Xiao Xu,
  • Xiao Xu,
  • Xiao Xu,
  • Xiao Xu,
  • Xiao Xu,
  • Xiao Xu,
  • Zeyan Li,
  • Zeyan Li,
  • Zeyan Li,
  • Zeyan Li,
  • Zeyan Li,
  • Zeyan Li,
  • Yuyang Zhou,
  • Yuyang Zhou,
  • Yuyang Zhou,
  • Yuyang Zhou,
  • Yuyang Zhou,
  • Yuyang Zhou,
  • Huixin Zhou,
  • Huixin Zhou,
  • Huixin Zhou,
  • Huixin Zhou,
  • Huixin Zhou,
  • Huixin Zhou,
  • Rui Li,
  • Rui Li,
  • Rui Li,
  • Rui Li,
  • Rui Li,
  • Rui Li,
  • Chen Peng,
  • Chen Peng,
  • Chen Peng,
  • Chen Peng,
  • Chen Peng,
  • Chen Peng,
  • Lilei Yu,
  • Lilei Yu,
  • Lilei Yu,
  • Lilei Yu,
  • Lilei Yu,
  • Lilei Yu,
  • Hong Jiang,
  • Hong Jiang,
  • Hong Jiang,
  • Hong Jiang,
  • Hong Jiang,
  • Hong Jiang

DOI
https://doi.org/10.3389/fcvm.2022.937608
Journal volume & issue
Vol. 9

Abstract

Read online

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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