title: Targeted disruption of the heat shock protein 20-phosphodiesterase 4D (PDE4D) interaction protects against pathological cardiac remodelling in a mouse model of hypertrophy.
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.
authors.affiliation: Institute of Medical, Veterinary and Life Sciences, University of Glasgow, Wolfson-Link Building, Glasgow G12 8QQ, UK.
authors.forename: Tamara P
authors.initials: TP
authors.lastname: Martin
authors.affiliation: Institute of Medical, Veterinary and Life Sciences, University of Glasgow, Wolfson-Link Building, Glasgow G12 8QQ, UK.
authors.forename: Maria P
authors.initials: MP
authors.lastname: Hortigon-Vinagre
authors.affiliation: Institute of Medical, Veterinary and Life Sciences, University of Glasgow, Wolfson-Link Building, Glasgow G12 8QQ, UK.
authors.forename: Jane E
authors.initials: JE
authors.lastname: Findlay
authors.affiliation: Institute of Medical, Veterinary and Life Sciences, University of Glasgow, Wolfson-Link Building, Glasgow G12 8QQ, UK.
authors.forename: Christina
authors.initials: C
authors.lastname: Elliott
authors.affiliation: Strathclyde Institute of Pharmacy & Biomedical Sciences, University of Strathclyde, Hamnett Building, 161 Cathedral Street, Glasgow G4 ORE, UK.
authors.forename: Susan
authors.initials: S
authors.lastname: Currie
authors.affiliation: Institute of Medical, Veterinary and Life Sciences, University of Glasgow, Wolfson-Link Building, Glasgow G12 8QQ, UK.
authors.forename: George S
authors.initials: GS
authors.lastname: Baillie
keywords: APD, action potential duration; Cardiac hypertrophy; Cardiac remodeling; FS, fractional shortening; HSP20; HSP20, heat shock protein 20; ISO, isoprenaline; LV, left ventricle; LVEDD, left ventricle end diastolic dimension; LVESD, left ventricle end systolic dimension; MTAB, minimally invasive transverse aortic banding; PBS, phosphate buffered saline; PDE4D; PDE4D, phosphodiesterase 4D; PKA, protein kinase-A; Peptide disruption; cAMP; hiPSC-CMs, human induced pluripotent stem cell-derived cardiac myocytes