Vagus nerve is crucially important in protecting the heart in myocardial infarction, preserving cardiac function in heart failure, and improving exercise capacity (Mastitskaya et al., 2012; Machhada et al., 2020). The signaling pathway from the vagus to the heart is complex and comprises a brain-gut-heart communication axis. The majority of vagal efferent fibers project to the gut where they control digestion and secretion of several gut hormones, including incretin hormone glucagon-like peptide-1 (GLP-1). GLP-1 exhibits substantial positive effects on the cardiovascular system – vasodilation, reduced inflammation, improved myocardial blood flow, and cardiomyocyte survival. Our research has shown that vagus nerve stimulation's cardioprotective action on the heart is mediated, at least in part, by an increased release of GLP-1 from the gut (Basalay et al., 2016; Mastitskaya et al., 2016). Stimulation of GLP-1 receptors in the heart leads to the activation of pro-survival signaling pathways (Basalay et al., 2016) and reduces myocardial susceptibility to ventricular arrhythmias (Ang et al., 2018). Additionally, vagus nerve stimulation prevents no-reflow after myocardial ischemia. No-reflow is a phenomenon when, after reopening of the culprit artery in myocardial infarction, blood flow at the microvascular level is not fully restored, heavily contributing to poor healing of the infarct, development of heart failure, malignant arrhythmias, and even cardiac rupture. Microvascular no-reflow is mediated by pericytes – contractile cells wrapped around capillaries. In ischemia, pericytes contract and constrict the underlying capillaries (O’Farrell et al., 2017). Our most recent data suggest that this constriction can be prevented by the stimulation of GLP-1Rs on microvasculature. The downstream molecular mechanism of GLP-1R activation involves the opening of KATP channels. GLP-1R agonists and KATP channel openers are therefore novel therapeutic targets to prevent no-reflow, reduce infarct size and decrease the incidence of ventricular arrhythmias in patients with ischaemic heart disease.
Regenerating the Cardiovascular System (University of Oxford, UK) (2023) Proc Physiol Soc 52, SA08
Research Symposium: Role of vagus nerve, incretin hormone GLP-1 and cardiac pericytes in cardioprotection against ischaemia/reperfusion injury
Svetlana Mastitskaya1,
1University College London London United Kingdom,
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Where applicable, experiments conform with Society ethical requirements.