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

Autor: Tamara P. Martin, Maria P. Hortigon-Vinagre, George S. Baillie, Susan Currie, Christina Elliott, Jane E. Findlay
Jazyk: angličtina
Rok vydání: 2014
Předmět:
MTAB
minimally invasive transverse aortic banding
medicine.medical_specialty
HSP20
heat shock protein 20
030204 cardiovascular system & hematology
PDE4D
Article
ISO
isoprenaline
PKA
protein kinase-A
General Biochemistry
Genetics and Molecular Biology
RS
Muscle hypertrophy
Contractility
03 medical and health sciences
0302 clinical medicine
PBS
phosphate buffered saline
APD
action potential duration
Internal medicine
Heat shock protein
cAMP
LVEDD
left ventricle end diastolic dimension
Medicine
Protein kinase A
Induced pluripotent stem cell
lcsh:QH301-705.5
030304 developmental biology
Cardiac remodeling
Pressure overload
0303 health sciences
FS
fractional shortening
business.industry
fungi
Phosphodiesterase
LVESD
left ventricle end systolic dimension
PDE4D
phosphodiesterase 4D
HSP20
Cardiac hypertrophy
LV
left ventricle
Endocrinology
lcsh:Biology (General)
Peptide disruption
Phosphorylation
hiPSC-CMs
human induced pluripotent stem cell-derived cardiac myocytes
business
Zdroj: FEBS Open Bio
FEBS Open Bio, Vol 4, Iss C, Pp 923-927 (2014)
ISSN: 2211-5463
Popis: Highlights • A peptide was discovered that disrupts HSP20–phosphodiesterase 4D (PDE4D) complex formation. • HSP20–PDE4D complex disruption reversed hypertrophic-induced changes in electrical signalling in human cardiac myocytes. • HSP20–PDE4D complex disruption attenuated the physiological response to pressure/volume overload. • This physiological response normally results in an increase in cardiac myocyte size. • Cardiac fibrosis was reduced in mice following treatment with the HSP20–PDE4D disruptor peptide.
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.
Databáze: OpenAIRE
Externí odkaz: