Molecular and cellular neurocardiology in heart disease

J Physiol. 2024 May 22. doi: 10.1113/JP284739. Online ahead of print.

Abstract

This paper updates and builds on a previous White Paper in this journal that some of us contributed to concerning the molecular and cellular basis of cardiac neurobiology of heart disease. Here we focus on recent findings that underpin cardiac autonomic development, novel intracellular pathways and neuroplasticity. Throughout we highlight unanswered questions and areas of controversy. Whilst some neurochemical pathways are already demonstrating prognostic viability in patients with heart failure, we also discuss the opportunity to better understand sympathetic impairment by using patient specific stem cells that provides pathophysiological contextualization to study 'disease in a dish'. Novel imaging techniques and spatial transcriptomics are also facilitating a road map for target discovery of molecular pathways that may form a therapeutic opportunity to treat cardiac dysautonomia.

Keywords: CamKII; autonomic nervous system; cardiac physiology; cardiovascular disease; induced pluripotent stem cells; neuron‐myocyte co‐cultures; optical mapping; optogenetics.