Targeted disruption of the heat shock protein 20–phosphodiesterase 4D (PDE4D) interaction protects against pathological cardiac remodelling in a mouse model of hypertrophy

Martin, T. P., Hortigon-Vinagre, M. P. , Findlay, J. E., Elliott, C., Currie, S. and Baillie, G. S. (2014) Targeted disruption of the heat shock protein 20–phosphodiesterase 4D (PDE4D) interaction protects against pathological cardiac remodelling in a mouse model of hypertrophy. FEBS Open Bio, 4, pp. 923-927. (doi:10.1016/j.fob.2014.10.011) (PMID:25426411) (PMCID:PMC4239479)

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Abstract

Phosphorylated heat shock protein 20 (HSP20) is cardioprotective. Using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and a mouse model of pressure overload mediated hypertrophy, we show that peptide disruption of the HSP20–phosphodiesterase 4D (PDE4D) complex results in attenuation of action potential prolongation and protection against adverse cardiac remodelling. The later was evidenced by improved contractility, decreased heart weight to body weight ratio, and reduced interstitial and perivascular fibrosis. This study demonstrates that disruption of the specific HSP20–PDE4D interaction leads to attenuation of pathological cardiac remodelling.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Baillie, Professor George and Elliott, Dr Christina and Findlay, Mrs Jane and Martin, Dr Tamara and Hortigon, Dr Maria
Authors: Martin, T. P., Hortigon-Vinagre, M. P., Findlay, J. E., Elliott, C., Currie, S., and Baillie, G. S.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:FEBS Open Bio
Publisher:Elsevier
ISSN:2211-5463
ISSN (Online):2211-5463
Copyright Holders:Copyright © 2014 The Authors
First Published:First published in FEBS Open Bio 4:923-927
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
582921Development of small molecules that induce the cardio-protective effects of HSP20George BaillieHeart Research UK (HEART-RES)RG2610/12/14RI CARDIOVASCULAR & MEDICAL SCIENCES
588611cAMP phosphodiesterase-4: signalling complexes, regulation and potential therapeutic targets.George BaillieMedical Research Council (MRC)MR/J007412/1RI CARDIOVASCULAR & MEDICAL SCIENCES