Imperial College London
Alternate

Emeritus ProfessorMichaelSchneider

Faculty of Medicine, National Heart & Lung Institute

Emeritus Professor in Cardiology
 
 
 
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Contact

 

+44 (0)013 34621727m.d.schneider Website

 
 
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Location

 

ICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Foldes:2014:10.1016/j.stemcr.2014.09.002,
author = {Foldes, G and Matsa, E and Kriston-Vizi, J and Leja, T and Amisten, S and Kolker, L and Kodagoda, T and Dolatshad, NF and Mioulane, M and Vauchez, K and Aranyi, T and Ketteler, R and Schneider, MD and Denning, C and Harding, SE},
doi = {10.1016/j.stemcr.2014.09.002},
journal = {Stem Cell Reports},
pages = {905--914},
title = {Aberrant alpha-adrenergic hypertrophic response in cardiomyocytes from human induced pluripotent cells},
url = {http://dx.doi.org/10.1016/j.stemcr.2014.09.002},
volume = {3},
year = {2014}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Cardiomyocytes from human embryonic stem cells (hESC-CMs) and induced pluripotent stem cells (hiPSC-CMs) represent new models for drug discovery. Although hypertrophy is a high-priority target, we found that hiPSC-CMs were systematically unresponsive to hypertrophic signals such as the α-adrenoceptor (αAR) agonist phenylephrine (PE) compared to hESC-CMs. We investigated signaling at multiple levels to understand the underlying mechanism of this differential responsiveness. The expression of the normal α1AR gene, ADRA1A, was reversibly silenced during differentiation, accompanied by ADRA1B upregulation in either cell type. ADRA1B signaling was intact in hESC-CMs, but not in hiPSC-CMs. We observed an increased tonic activity of inhibitory kinase pathways in hiPSC-CMs, and inhibition of antihypertrophic kinases revealed hypertrophic increases. There is tonic suppression of cell growth in hiPSC-CMs, but not hESC-CMs, limiting their use in investigation of hypertrophic signaling. These data raise questions regarding the hiPSC-CM as a valid model for certain aspects of cardiac disease.
AU  - Foldes,G
AU  - Matsa,E
AU  - Kriston-Vizi,J
AU  - Leja,T
AU  - Amisten,S
AU  - Kolker,L
AU  - Kodagoda,T
AU  - Dolatshad,NF
AU  - Mioulane,M
AU  - Vauchez,K
AU  - Aranyi,T
AU  - Ketteler,R
AU  - Schneider,MD
AU  - Denning,C
AU  - Harding,SE
DO  - 10.1016/j.stemcr.2014.09.002
EP  - 914
PY  - 2014///
SN  - 2213-6711
SP  - 905
TI  - Aberrant alpha-adrenergic hypertrophic response in cardiomyocytes from human induced pluripotent cells
T2  - Stem Cell Reports
UR  - http://dx.doi.org/10.1016/j.stemcr.2014.09.002
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000345118600018&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - http://hdl.handle.net/10044/1/21750
VL  - 3
ER  -
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