Mediation of Cardiac Macrophage Activity <i>via</i> Auricular Vagal Nerve Stimulation Ameliorates Cardiac Ischemia/Reperfusion Injury

Author: Chee Hooi Chung1, Beatrice Bretherton2, Satirah Zainalabidin3, Susan A Deuchars2, Jim Deuchars2, Mohd Kaisan Mahadi1
1 Drug and Herbal Research Centre, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.
2 School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds, United Kingdom.
3 Programme of Biomedical Science, Center for Toxicology and Health Risk Study (CORE), Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.
Conference/Journal: Front Neurosci
Date published: 2020 Sep 8
Other: Volume ID: 14 , Pages: 906 , Special Notes: doi: 10.3389/fnins.2020.00906. , Word Count: 254

Myocardial infarction (MI) reperfusion therapy causes paradoxical cardiac complications. Following restoration of blood flow to infarcted regions, a multitude of inflammatory cells are recruited to the site of injury for tissue repair. Continual progression of cardiac inflammatory responses does, however, lead to adverse cardiac remodeling, inevitably causing heart failure.

Main body:
Increasing evidence of the cardioprotective effects of both invasive and non-invasive vagal nerve stimulation (VNS) suggests that these may be feasible methods to treat myocardial ischemia/reperfusion injury via anti-inflammatory regulation. The mechanisms through which auricular VNS controls inflammation are yet to be explored. In this review, we discuss the potential of autonomic nervous system modulation, particularly via the parasympathetic branch, in ameliorating MI. Novel insights are provided about the activation of the cholinergic anti-inflammatory pathway on cardiac macrophages. Acetylcholine binding to the α7 nicotinic acetylcholine receptor (α7nAChR) expressed on macrophages polarizes the pro-inflammatory into anti-inflammatory subtypes. Activation of the α7nAChR stimulates the signal transducer and activator of transcription 3 (STAT3) signaling pathway. This inhibits the secretion of pro-inflammatory cytokines, limiting ischemic injury in the myocardium and initiating efficient reparative mechanisms. We highlight recent developments in the controversial auricular vagal neuro-circuitry and how they may relate to activation of the cholinergic anti-inflammatory pathway.

Emerging published data suggest that auricular VNS is an inexpensive healthcare modality, mediating the dynamic balance between pro- and anti-inflammatory responses in cardiac macrophages and ameliorating cardiac ischemia/reperfusion injury.

Keywords: auricular vagal nerve stimulation; cholinergic anti-inflammatory pathway; ischemia/reperfusion injury; macrophage polarization; myocardial infarction.

PMID: 33013299 PMCID: PMC7506070 DOI: 10.3389/fnins.2020.00906