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Metabolism regulator adiponectin prevents cardiac remodeling and ventricular arrhythmias via sympathetic modulation in a myocardial infarction model

Abstract

The stellate ganglia play an important role in cardiac remodeling after myocardial infarction (MI). This study aimed to investigate whether adiponectin (APN), an adipokine mainly secreted by adipose tissue, could modulate the left stellate ganglion (LSG) and exert cardioprotective effects through the sympathetic nervous system (SNS) in a canine model of MI. APN microinjection and APN overexpression with recombinant adeno-associated virus vector in the LSG were performed in acute and chronic MI models, respectively. The results showed that acute APN microinjection decreased LSG function and neural activity, and suppressed ischemia-induced ventricular arrhythmia. Chronic MI led to a decrease in the effective refractory period and action potential duration at 90% and deterioration in echocardiography performance, all of which was blunted by APN overexpression. Moreover, APN gene transfer resulted in favorable heart rate variability alteration, and decreased cardiac SNS activity, serum noradrenaline and neuropeptide Y, which were augmented after MI. APN overexpression also decreased the expression of nerve growth factor and growth associated protein 43 in the LSG and peri-infarct myocardium, respectively. Furthermore, RNA sequencing of LSG indicated that 4-week MI up-regulated the mRNA levels of macrophage/microglia activation marker Iba1, chemokine ligands (CXCL10, CCL20), chemokine receptor CCR5 and pro-inflammatory cytokine IL6, and downregulated IL1RN and IL10 mRNA, which were reversed by APN overexpression. Our results reveal that APN inhibits cardiac sympathetic remodeling and mitigates cardiac remodeling after MI. APN-mediated gene therapy may provide a potential therapeutic strategy for the treatment of MI.

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Data availability

The datasets are available on reasonable request to the corresponding author.

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Funding

This work was supported by the National Natural Science Foundation of China [81871486, 81970287 and 82100530], and Foundation for Innovative Research Groups of Natural Science Foundation of Hubei Province, China (2021CFA010).

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ZZ, LY and HJ designed the study. CL, SX, SD, QD and JS conducted the study. ZZ, JW, FY, FG and YZ analyzed the data. ZZ, MW, YW, and LZ drafted the manuscript. All authors have approved the manuscript.

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Correspondence to Hong Jiang or Lilei Yu.

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The authors declare no competing financial interests.

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Zhou, Z., Liu, C., Xu, S. et al. Metabolism regulator adiponectin prevents cardiac remodeling and ventricular arrhythmias via sympathetic modulation in a myocardial infarction model. Basic Res Cardiol 117, 34 (2022). https://doi.org/10.1007/s00395-022-00939-2

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  • DOI: https://doi.org/10.1007/s00395-022-00939-2

Keywords

  • Left stellate ganglion
  • Adiponectin
  • Myocardial infarction
  • Sympathetic nervous system
  • Cardiac remodeling
  • Ventricular arrhythmia