Brain-gut-heart communication axis in cardioprotection

Abstract

Vagal tone has long been associated with cardiac health. Recently, we have demonstrated that cardioprotective action of vagus nerve is attributed to the neurones of the dorsal motor nucleus of the vagus (DMV). Optogenetic stimulation of DMV neurones results in a significant reduction of infarct size in ischaemia/reperfusion injury (Cardiovasc Res 95:487, 2012), as well as preserves ejection fraction and exercise capacity in chronic heart failure model (JACC Basic Transl Sci 5:799, 2020). Cardioprotective action of DMV neurones can be evoked acutely by a procedure called remote ischaemic preconditioning (RIPC) – short episodes of non-lethal ischaemia to a remote organ preceding subsequent long ischaemic insult to the myocardium. We have discovered that this innate phenomenon of potent interorgan protection recruits autonomic reflexes and involves gut-brain-heart communication axis acting via DMV projections to the gut and glucagon-like peptide 1 as an effector molecule (PLoS One 11:e0150108, 2016; Cardiovasc Res 112:669, 2016). GLP-1 action on the heart is indirect, is mediated via acetylcholine and NO, and, among others, includes activation of survival kinases (Cardiovasc Res 112:669, 2016) and modulation of cardiac ventricular excitability (Circ Arrhythm Electrophysiol 11:e006740, 2018). These indirect GLP-1-mediated effects of DMV-to-gut signaling on the heart may indicate a role for the gut as an endocrine arm of the parasympathetic nervous system (Front Neurosci 13:1008, 2019), just like adrenal gland for the sympathetic nervous system. Such reimagining of the gut’s role in vagal control may help to further understand the importance of brain-gut axis in various processes, including metabolic disorders, cardiovascular pathology and tumour growth.