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.
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.