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Mast cell stabilizer, an anti-allergic drug, reduces ventricular arrhythmia risk via modulation of neuroimmune interaction

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Abstract

Mast cells (MCs) are important intermediates between the nervous and immune systems. The cardiac autonomic nervous system (CANS) crucially modulates cardiac electrophysiology and arrhythmogenesis, but whether and how MC-CANS neuroimmune interaction influences arrhythmia remain unclear. Our clinical data showed a close relationship between serum levels of MC markers and CANS activity, and then we use mast cell stabilizers (MCSs) to alter this MC-CANS communication. MCSs, which are well-known anti-allergic agents, could reduce the risk of ventricular arrhythmia (VA) after myocardial infarction (MI). RNA-sequencing (RNA-seq) analysis to investigate the underlying mechanism by which MCSs could affect the left stellate ganglion (LSG), a key therapeutic target for modulating CANS, showed that the IL-6 and γ-aminobutyric acid (GABA)-ergic system may be involved in this process. Our findings demonstrated that MCSs reduce VA risk along with revealing the potential underlying antiarrhythmic mechanisms.

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Data availability

All data are available in the main text or the supplementary materials.

Abbreviations

VA:

Ventricular arrhythmia

CANS:

Cardiac autonomic nervous system

LSG:

Left stellate ganglion

MI:

Myocardial infarction

MC:

Mast cell

MCS:

MC stabilizer

GABA:

γ-Aminobutyric acid

AAV:

Adeno-Associated Virus

SBP:

Systolic blood pressure

ERP:

Effective refractory period

VPB:

Ventricular premature beat

LVA:

Left ventricular apex

LVB:

Left ventricular base

LVM:

Left mid ventricle

HRV:

Heart rate variability

SDNN:

Standard deviation of the NN intervals

SDANN:

Standard deviation of the average NN intervals

DC:

Deceleration capacity

SCD:

Sudden cardiac death

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Acknowledgements

Y.W., H.J., and L.Y. conceived the experiments. Y.W., Z.L., and L.Y. wrote the paper. All authors performed animal experiments. Y.W., Z.L., W.Z., J.W., R.L., J.S., Q.D., S.D., W.T., Y.W., and L.S. collected human data. Y.W. and Z.L. analyzed the data. H.J. and L.Y. secured funding.

Funding

This work was supported by the grants from National Natural Science Foundation of China (No. 82270532, 82241057, 82370286), Foundation for Innovative Research Groups of Natural Science Foundation of Hubei Province, China (2021CFA010) (Grant no. 82100530), and the Open Project of Hubei Key Laboratory (Grant no. 2023KFZZ019).

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  1. Yuhong Wang and Zhihao Liu contributed equally to the study.

Authors and Affiliations

  1. Department of Cardiology, Renmin Hospital of Wuhan University, Hubei Key Laboratory of Autonomic Nervous System Modulation, Cardiac Autonomic Nervous System Research Center of Wuhan University, Taikang Center for Life and Medical Sciences of Wuhan University, Hubei Key Laboratory of Cardiology, Cardiovascular Research Institute of Wuhan University, No. 238 Jiefang Road, Wuchang District, Wuhan City, 430060, Hubei Province, People’s Republic of China

    Yuhong Wang, Zhihao Liu, Wenjie Zhou, Jun Wang, Rui Li, Chen Peng, Liying Jiao, Song Zhang, Zhihao Liu, Zhongyang Yu, Ji Sun, Qiang Deng, Shoupeng Duan, Wuping Tan, Yijun Wang, Lingpeng Song, Fuding Guo, Zhen Zhou, Yueyi Wang, Liping Zhou, Hong Jiang & Lilei Yu

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  1. Yuhong Wang
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Wang, Y., Liu, Z., Zhou, W. et al. Mast cell stabilizer, an anti-allergic drug, reduces ventricular arrhythmia risk via modulation of neuroimmune interaction. Basic Res Cardiol 119, 75–91 (2024). https://doi.org/10.1007/s00395-023-01024-y

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