Pathophysiological mechanisms of sino-atrial dysfunction and ventricular conduction disease associated with SCN5A deficiency:Insights from mouse models

Huang, Christopher L.H., Lei, Lily, Matthews, Gareth D.K. ORCID: https://orcid.org/0000-0001-8353-4806, Zhang, Yanmin and Lei, Ming (2012) Pathophysiological mechanisms of sino-atrial dysfunction and ventricular conduction disease associated with SCN5A deficiency:Insights from mouse models. Frontiers in Physiology, 3 JUL. ISSN 1664-042X

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Abstract

Genetically modified mice provide a numberofmodels for studying cardiac channelopathies related to cardiac Na + channel (SCN5A) abnormalities. We review key pathophysiologi-cal features in these murine models that may underlie clinical features observed in sinus node dysfunction and progressive cardiac conduction disease, thereby providing insights into their pathophysiological mechanisms. We describe loss of Na + channel function and fibrotic changes associated with both loss and gain-of-function Na + channel mutations. Recent reports further relate the progressive fibrotic changes to upregulation of TGF-β1 production and the transcription factors, Atf3, a stress-inducible gene, and Egr1, to the presence of heterozygous Scn5a gene deletion. Both changes are thus directly implicated in the clinically observed disruptions in sino-atrial node pacemaker function, and sino-atrial and ventricular conduction, and their progression with age. Murine systems with genetic modifications in Scn5a thus prove a useful tool to address questions concerning roles of genetic and environmental modifiers on human SCN5A disease phenotypes.

Item Type:	Article
Uncontrolled Keywords:	mouse genetic models,progressive cardiac conduction disease,scn5a,sinus node dysfunction,physiology,physiology (medical),sdg 3 - good health and well-being ,/dk/atira/pure/subjectarea/asjc/1300/1314
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School
Related URLs:	http://www.scopus.com/inward/record.url?...
Depositing User:	LivePure Connector
Date Deposited:	10 Nov 2022 13:30
Last Modified:	15 Nov 2022 10:30
URI:	https://ueaeprints.uea.ac.uk/id/eprint/89773
DOI:	10.3389/fphys.2012.00234

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