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)

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 > School of Cardiovascular & Metabolic Health
• 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

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
58292	1	Development of small molecules that induce the cardio-protective effects of HSP20	George Baillie	Heart Research UK (HEART-RES)	RG2610/12/14	RI CARDIOVASCULAR & MEDICAL SCIENCES
58861	1	cAMP phosphodiesterase-4: signalling complexes, regulation and potential therapeutic targets.	George Baillie	Medical Research Council (MRC)	MR/J007412/1	RI CARDIOVASCULAR & MEDICAL SCIENCES