Cargando…

Aberrant α-Adrenergic Hypertrophic Response in Cardiomyocytes from Human Induced Pluripotent Cells

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-adrenocepto...

Descripción completa

Detalles Bibliográficos
Autores principales: Földes, Gabor, Matsa, Elena, Kriston-Vizi, János, Leja, Thomas, Amisten, Stefan, Kolker, Ljudmila, Kodagoda, Thusharika, Dolatshad, Nazanin F., Mioulane, Maxime, Vauchez, Karine, Arányi, Tamás, Ketteler, Robin, Schneider, Michael D., Denning, Chris, Harding, Sian E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4235744/
https://www.ncbi.nlm.nih.gov/pubmed/25418732
http://dx.doi.org/10.1016/j.stemcr.2014.09.002
_version_ 1782345072762683392
author Földes, Gabor
Matsa, Elena
Kriston-Vizi, János
Leja, Thomas
Amisten, Stefan
Kolker, Ljudmila
Kodagoda, Thusharika
Dolatshad, Nazanin F.
Mioulane, Maxime
Vauchez, Karine
Arányi, Tamás
Ketteler, Robin
Schneider, Michael D.
Denning, Chris
Harding, Sian E.
author_facet Földes, Gabor
Matsa, Elena
Kriston-Vizi, János
Leja, Thomas
Amisten, Stefan
Kolker, Ljudmila
Kodagoda, Thusharika
Dolatshad, Nazanin F.
Mioulane, Maxime
Vauchez, Karine
Arányi, Tamás
Ketteler, Robin
Schneider, Michael D.
Denning, Chris
Harding, Sian E.
author_sort Földes, Gabor
collection PubMed
description 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 α(1)AR 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.
format Online
Article
Text
id pubmed-4235744
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher Elsevier
record_format MEDLINE/PubMed
spelling pubmed-42357442014-11-19 Aberrant α-Adrenergic Hypertrophic Response in Cardiomyocytes from Human Induced Pluripotent Cells Földes, Gabor Matsa, Elena Kriston-Vizi, János Leja, Thomas Amisten, Stefan Kolker, Ljudmila Kodagoda, Thusharika Dolatshad, Nazanin F. Mioulane, Maxime Vauchez, Karine Arányi, Tamás Ketteler, Robin Schneider, Michael D. Denning, Chris Harding, Sian E. Stem Cell Reports Resource 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 α(1)AR 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. Elsevier 2014-10-11 /pmc/articles/PMC4235744/ /pubmed/25418732 http://dx.doi.org/10.1016/j.stemcr.2014.09.002 Text en © 2014 The Authors http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).
spellingShingle Resource
Földes, Gabor
Matsa, Elena
Kriston-Vizi, János
Leja, Thomas
Amisten, Stefan
Kolker, Ljudmila
Kodagoda, Thusharika
Dolatshad, Nazanin F.
Mioulane, Maxime
Vauchez, Karine
Arányi, Tamás
Ketteler, Robin
Schneider, Michael D.
Denning, Chris
Harding, Sian E.
Aberrant α-Adrenergic Hypertrophic Response in Cardiomyocytes from Human Induced Pluripotent Cells
title Aberrant α-Adrenergic Hypertrophic Response in Cardiomyocytes from Human Induced Pluripotent Cells
title_full Aberrant α-Adrenergic Hypertrophic Response in Cardiomyocytes from Human Induced Pluripotent Cells
title_fullStr Aberrant α-Adrenergic Hypertrophic Response in Cardiomyocytes from Human Induced Pluripotent Cells
title_full_unstemmed Aberrant α-Adrenergic Hypertrophic Response in Cardiomyocytes from Human Induced Pluripotent Cells
title_short Aberrant α-Adrenergic Hypertrophic Response in Cardiomyocytes from Human Induced Pluripotent Cells
title_sort aberrant α-adrenergic hypertrophic response in cardiomyocytes from human induced pluripotent cells
topic Resource
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4235744/
https://www.ncbi.nlm.nih.gov/pubmed/25418732
http://dx.doi.org/10.1016/j.stemcr.2014.09.002
work_keys_str_mv AT foldesgabor aberrantaadrenergichypertrophicresponseincardiomyocytesfromhumaninducedpluripotentcells
AT matsaelena aberrantaadrenergichypertrophicresponseincardiomyocytesfromhumaninducedpluripotentcells
AT kristonvizijanos aberrantaadrenergichypertrophicresponseincardiomyocytesfromhumaninducedpluripotentcells
AT lejathomas aberrantaadrenergichypertrophicresponseincardiomyocytesfromhumaninducedpluripotentcells
AT amistenstefan aberrantaadrenergichypertrophicresponseincardiomyocytesfromhumaninducedpluripotentcells
AT kolkerljudmila aberrantaadrenergichypertrophicresponseincardiomyocytesfromhumaninducedpluripotentcells
AT kodagodathusharika aberrantaadrenergichypertrophicresponseincardiomyocytesfromhumaninducedpluripotentcells
AT dolatshadnazaninf aberrantaadrenergichypertrophicresponseincardiomyocytesfromhumaninducedpluripotentcells
AT mioulanemaxime aberrantaadrenergichypertrophicresponseincardiomyocytesfromhumaninducedpluripotentcells
AT vauchezkarine aberrantaadrenergichypertrophicresponseincardiomyocytesfromhumaninducedpluripotentcells
AT aranyitamas aberrantaadrenergichypertrophicresponseincardiomyocytesfromhumaninducedpluripotentcells
AT kettelerrobin aberrantaadrenergichypertrophicresponseincardiomyocytesfromhumaninducedpluripotentcells
AT schneidermichaeld aberrantaadrenergichypertrophicresponseincardiomyocytesfromhumaninducedpluripotentcells
AT denningchris aberrantaadrenergichypertrophicresponseincardiomyocytesfromhumaninducedpluripotentcells
AT hardingsiane aberrantaadrenergichypertrophicresponseincardiomyocytesfromhumaninducedpluripotentcells