Evidence map›Paper›PMID 25504561›Full record

ArticleCirculation. Arrhythmia and electrophysiology2015

Phospholamban as a crucial determinant of the inotropic response of human pluripotent stem cell-derived ventricular cardiomyocytes and engineered 3-dimensional tissue constructs.

Gaopeng Chen, Sen Li, Ioannis Karakikes, Lihuan Ren, Maggie Zi-Ying Chow, Anant Chopra, Wendy Keung, Bin Yan, Camie W Y Chan, Kevin D Costa and 4 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Circulation. Arrhythmia and electrophysiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
1.0field-weighted citation impact, top 24% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

21 citing papers in PubMed, 37 citations in OpenAlex.

  1. Article
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  6. Article
  7. Review
  8. Review
  9. Engineered Heart Muscle Models in Phenotypic Drug Screens.Handbook of experimental pharmacology · 2021
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  10. CaCell calcium · 2020
    Review
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Human ISL1Molecular therapy : the journal of the American Society of Gene Therapy · 2018
    Article
  17. Article
  18. Review
  19. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 2 institutions in 1 country.

Gaopeng ChenFrom the Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, Manhattan, NY (G.C., I.K., K.D.C., R.J.H., R.A.L.); Department of Physiology (G.C., S.L., L.R., M.Z.-Y.C., W.K., C.-W.K., R.A.L.), Stem Cell and Regenerative Medicine Consortium (G.C., S.L., L.R., M.Z.-Y.C., W.K., B.Y., C.W.Y.C., C.-W.K., R.A.L.), Department of Anatomy (C.W.Y.C.), LKS Faculty of Medicine, University of Hong Kong, Pokfulam, Hong Kong; Department of Bioengineering, Boston University, MA (A.C., C.S.C.); Harvard Wyss Institute for Biologically Inspired Engineering, Boston, MA (A.C., C.S.C.); and Department of Biology, Hong Kong Baptist University, Hong Kong (B.Y.).
Sen LiFrom the Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, Manhattan, NY (G.C., I.K., K.D.C., R.J.H., R.A.L.); Department of Physiology (G.C., S.L., L.R., M.Z.-Y.C., W.K., C.-W.K., R.A.L.), Stem Cell and Regenerative Medicine Consortium (G.C., S.L., L.R., M.Z.-Y.C., W.K., B.Y., C.W.Y.C., C.-W.K., R.A.L.), Department of Anatomy (C.W.Y.C.), LKS Faculty of Medicine, University of Hong Kong, Pokfulam, Hong Kong; Department of Bioengineering, Boston University, MA (A.C., C.S.C.); Harvard Wyss Institute for Biologically Inspired Engineering, Boston, MA (A.C., C.S.C.); and Department of Biology, Hong Kong Baptist University, Hong Kong (B.Y.).
Ioannis KarakikesFrom the Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, Manhattan, NY (G.C., I.K., K.D.C., R.J.H., R.A.L.); Department of Physiology (G.C., S.L., L.R., M.Z.-Y.C., W.K., C.-W.K., R.A.L.), Stem Cell and Regenerative Medicine Consortium (G.C., S.L., L.R., M.Z.-Y.C., W.K., B.Y., C.W.Y.C., C.-W.K., R.A.L.), Department of Anatomy (C.W.Y.C.), LKS Faculty of Medicine, University of Hong Kong, Pokfulam, Hong Kong; Department of Bioengineering, Boston University, MA (A.C., C.S.C.); Harvard Wyss Institute for Biologically Inspired Engineering, Boston, MA (A.C., C.S.C.); and Department of Biology, Hong Kong Baptist University, Hong Kong (B.Y.).
Lihuan RenFrom the Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, Manhattan, NY (G.C., I.K., K.D.C., R.J.H., R.A.L.); Department of Physiology (G.C., S.L., L.R., M.Z.-Y.C., W.K., C.-W.K., R.A.L.), Stem Cell and Regenerative Medicine Consortium (G.C., S.L., L.R., M.Z.-Y.C., W.K., B.Y., C.W.Y.C., C.-W.K., R.A.L.), Department of Anatomy (C.W.Y.C.), LKS Faculty of Medicine, University of Hong Kong, Pokfulam, Hong Kong; Department of Bioengineering, Boston University, MA (A.C., C.S.C.); Harvard Wyss Institute for Biologically Inspired Engineering, Boston, MA (A.C., C.S.C.); and Department of Biology, Hong Kong Baptist University, Hong Kong (B.Y.).
Maggie Zi-Ying ChowFrom the Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, Manhattan, NY (G.C., I.K., K.D.C., R.J.H., R.A.L.); Department of Physiology (G.C., S.L., L.R., M.Z.-Y.C., W.K., C.-W.K., R.A.L.), Stem Cell and Regenerative Medicine Consortium (G.C., S.L., L.R., M.Z.-Y.C., W.K., B.Y., C.W.Y.C., C.-W.K., R.A.L.), Department of Anatomy (C.W.Y.C.), LKS Faculty of Medicine, University of Hong Kong, Pokfulam, Hong Kong; Department of Bioengineering, Boston University, MA (A.C., C.S.C.); Harvard Wyss Institute for Biologically Inspired Engineering, Boston, MA (A.C., C.S.C.); and Department of Biology, Hong Kong Baptist University, Hong Kong (B.Y.).
Anant ChopraFrom the Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, Manhattan, NY (G.C., I.K., K.D.C., R.J.H., R.A.L.); Department of Physiology (G.C., S.L., L.R., M.Z.-Y.C., W.K., C.-W.K., R.A.L.), Stem Cell and Regenerative Medicine Consortium (G.C., S.L., L.R., M.Z.-Y.C., W.K., B.Y., C.W.Y.C., C.-W.K., R.A.L.), Department of Anatomy (C.W.Y.C.), LKS Faculty of Medicine, University of Hong Kong, Pokfulam, Hong Kong; Department of Bioengineering, Boston University, MA (A.C., C.S.C.); Harvard Wyss Institute for Biologically Inspired Engineering, Boston, MA (A.C., C.S.C.); and Department of Biology, Hong Kong Baptist University, Hong Kong (B.Y.).
Wendy KeungFrom the Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, Manhattan, NY (G.C., I.K., K.D.C., R.J.H., R.A.L.); Department of Physiology (G.C., S.L., L.R., M.Z.-Y.C., W.K., C.-W.K., R.A.L.), Stem Cell and Regenerative Medicine Consortium (G.C., S.L., L.R., M.Z.-Y.C., W.K., B.Y., C.W.Y.C., C.-W.K., R.A.L.), Department of Anatomy (C.W.Y.C.), LKS Faculty of Medicine, University of Hong Kong, Pokfulam, Hong Kong; Department of Bioengineering, Boston University, MA (A.C., C.S.C.); Harvard Wyss Institute for Biologically Inspired Engineering, Boston, MA (A.C., C.S.C.); and Department of Biology, Hong Kong Baptist University, Hong Kong (B.Y.).
Bin YanFrom the Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, Manhattan, NY (G.C., I.K., K.D.C., R.J.H., R.A.L.); Department of Physiology (G.C., S.L., L.R., M.Z.-Y.C., W.K., C.-W.K., R.A.L.), Stem Cell and Regenerative Medicine Consortium (G.C., S.L., L.R., M.Z.-Y.C., W.K., B.Y., C.W.Y.C., C.-W.K., R.A.L.), Department of Anatomy (C.W.Y.C.), LKS Faculty of Medicine, University of Hong Kong, Pokfulam, Hong Kong; Department of Bioengineering, Boston University, MA (A.C., C.S.C.); Harvard Wyss Institute for Biologically Inspired Engineering, Boston, MA (A.C., C.S.C.); and Department of Biology, Hong Kong Baptist University, Hong Kong (B.Y.).
Camie W Y ChanFrom the Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, Manhattan, NY (G.C., I.K., K.D.C., R.J.H., R.A.L.); Department of Physiology (G.C., S.L., L.R., M.Z.-Y.C., W.K., C.-W.K., R.A.L.), Stem Cell and Regenerative Medicine Consortium (G.C., S.L., L.R., M.Z.-Y.C., W.K., B.Y., C.W.Y.C., C.-W.K., R.A.L.), Department of Anatomy (C.W.Y.C.), LKS Faculty of Medicine, University of Hong Kong, Pokfulam, Hong Kong; Department of Bioengineering, Boston University, MA (A.C., C.S.C.); Harvard Wyss Institute for Biologically Inspired Engineering, Boston, MA (A.C., C.S.C.); and Department of Biology, Hong Kong Baptist University, Hong Kong (B.Y.).
Kevin D CostaFrom the Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, Manhattan, NY (G.C., I.K., K.D.C., R.J.H., R.A.L.); Department of Physiology (G.C., S.L., L.R., M.Z.-Y.C., W.K., C.-W.K., R.A.L.), Stem Cell and Regenerative Medicine Consortium (G.C., S.L., L.R., M.Z.-Y.C., W.K., B.Y., C.W.Y.C., C.-W.K., R.A.L.), Department of Anatomy (C.W.Y.C.), LKS Faculty of Medicine, University of Hong Kong, Pokfulam, Hong Kong; Department of Bioengineering, Boston University, MA (A.C., C.S.C.); Harvard Wyss Institute for Biologically Inspired Engineering, Boston, MA (A.C., C.S.C.); and Department of Biology, Hong Kong Baptist University, Hong Kong (B.Y.).
Chi-Wing KongFrom the Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, Manhattan, NY (G.C., I.K., K.D.C., R.J.H., R.A.L.); Department of Physiology (G.C., S.L., L.R., M.Z.-Y.C., W.K., C.-W.K., R.A.L.), Stem Cell and Regenerative Medicine Consortium (G.C., S.L., L.R., M.Z.-Y.C., W.K., B.Y., C.W.Y.C., C.-W.K., R.A.L.), Department of Anatomy (C.W.Y.C.), LKS Faculty of Medicine, University of Hong Kong, Pokfulam, Hong Kong; Department of Bioengineering, Boston University, MA (A.C., C.S.C.); Harvard Wyss Institute for Biologically Inspired Engineering, Boston, MA (A.C., C.S.C.); and Department of Biology, Hong Kong Baptist University, Hong Kong (B.Y.).
Roger J HajjarFrom the Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, Manhattan, NY (G.C., I.K., K.D.C., R.J.H., R.A.L.); Department of Physiology (G.C., S.L., L.R., M.Z.-Y.C., W.K., C.-W.K., R.A.L.), Stem Cell and Regenerative Medicine Consortium (G.C., S.L., L.R., M.Z.-Y.C., W.K., B.Y., C.W.Y.C., C.-W.K., R.A.L.), Department of Anatomy (C.W.Y.C.), LKS Faculty of Medicine, University of Hong Kong, Pokfulam, Hong Kong; Department of Bioengineering, Boston University, MA (A.C., C.S.C.); Harvard Wyss Institute for Biologically Inspired Engineering, Boston, MA (A.C., C.S.C.); and Department of Biology, Hong Kong Baptist University, Hong Kong (B.Y.).
Christopher S ChenFrom the Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, Manhattan, NY (G.C., I.K., K.D.C., R.J.H., R.A.L.); Department of Physiology (G.C., S.L., L.R., M.Z.-Y.C., W.K., C.-W.K., R.A.L.), Stem Cell and Regenerative Medicine Consortium (G.C., S.L., L.R., M.Z.-Y.C., W.K., B.Y., C.W.Y.C., C.-W.K., R.A.L.), Department of Anatomy (C.W.Y.C.), LKS Faculty of Medicine, University of Hong Kong, Pokfulam, Hong Kong; Department of Bioengineering, Boston University, MA (A.C., C.S.C.); Harvard Wyss Institute for Biologically Inspired Engineering, Boston, MA (A.C., C.S.C.); and Department of Biology, Hong Kong Baptist University, Hong Kong (B.Y.).
Ronald A LiFrom the Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, Manhattan, NY (G.C., I.K., K.D.C., R.J.H., R.A.L.); Department of Physiology (G.C., S.L., L.R., M.Z.-Y.C., W.K., C.-W.K., R.A.L.), Stem Cell and Regenerative Medicine Consortium (G.C., S.L., L.R., M.Z.-Y.C., W.K., B.Y., C.W.Y.C., C.-W.K., R.A.L.), Department of Anatomy (C.W.Y.C.), LKS Faculty of Medicine, University of Hong Kong, Pokfulam, Hong Kong; Department of Bioengineering, Boston University, MA (A.C., C.S.C.); Harvard Wyss Institute for Biologically Inspired Engineering, Boston, MA (A.C., C.S.C.); and Department of Biology, Hong Kong Baptist University, Hong Kong (B.Y.). ronaldli@hku.hk.
Icahn School of Medicine at Mount Sinai · USBoston University · US

Funding

SUMO1 and SERCA2a FunctionR01HL117505 · NHLBI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI WEBER, THOMAS · 2013 to 2020
$3.4M
Targeting Abnormal Calcium Cycling Using Novel Gene Therapy VectorsR01HL119046 · NHLBI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI AKAR, FADI GABRIEL, HAJJAR, ROGER J. · 2014 to 2017
$2.9M
Role of miR25 in Heart FailureR01HL128072 · NHLBI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI HAJJAR, ROGER J., MERCOLA, MARK · 2015 to 2018
$2.5M
Regression of cardiac hypertrophyR01HL093183 · NHLBI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI HAJJAR, ROGER J. · 2009 to 2010
$1.1M
NHLBI NIH HHS R01 HL093183NHLBI NIH HHS R01 HL117505NHLBI NIH HHS R01 HL119046NHLBI NIH HHS R01 HL128072
6 · The paper itself

Abstract

backgroundHuman (h) embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) serve as a potential unlimited ex vivo source of cardiomyocytes (CMs). However, a well-accepted roadblock has been their immature phenotype. hESC/iPSC-derived ventricular (v) CMs and their engineered cardiac microtissues (hvCMTs) similarly displayed positive chronotropic but null inotropic responses to β-adrenergic stimulation. Given that phospholamban (PLB) is robustly present in adult but poorly expressed in hESC/iPSC-vCMs and its defined biological role in β-adrenergic signaling, we investigated the functional consequences of PLB expression in hESC/iPSC-vCMs and hvCMTs. METHODS AND

resultsFirst, we confirmed that PLB protein was differentially expressed in hESC (HES2, H9)- and iPSC-derived and adult vCMs. We then transduced hES2-vCMs with the recombinant adenoviruses (Ad) Ad-PLB or Ad-S16E-PLB to overexpress wild-type PLB or the pseudophosphorylated point-mutated variant, respectively. As anticipated from the inhibitory effect of unphosphorylated PLB on sarco/endoplasmic reticulum Ca2+-ATPase, Ad-PLB transduction significantly attenuated electrically evoked Ca2+ transient amplitude and prolonged the 50% decay time. Importantly, Ad-PLB-transduced hES2-vCMs uniquely responded to isoproterenol. Ad-S16E-PLB-transduced hES2-vCMs displayed an intermediate phenotype. The same trends were observed with H9- and iPSC-vCMs. Directionally, similar results were also seen with Ad-PLB-transduced and Ad-S16E-transduced hvCMTs. However, Ad-PLB altered neither the global transcriptome nor ICa,L, implicating a PLB-specific effect.

conclusionsEngineered upregulation of PLB expression in hESC/iPSC-vCMs restores a positive inotropic response to β-adrenergic stimulation. These results not only provide a better mechanistic understanding of the immaturity of hESC/iPSC-vCMs but will also lead to improved disease models and transplantable prototypes with adult-like physiological responses.

Indexed as

Cell DifferentiationMyocardial ContractionAdrenergic beta-AgonistsCalcium-Binding ProteinsCalcium SignalingCells, CulturedCoculture TechniquesEmbryonic Stem CellsHumansInduced Pluripotent Stem CellsIsoproterenolMutationMyocytes, CardiacPhenotypePhospholambanSarcoplasmic ReticulumAdrenergic beta-AgonistsCalcium-Binding ProteinsIsoproterenolPhospholambanSarcoplasmic Reticulum Calcium-Transporting ATPasesadrenergic effectsphospholambanpluripotent stem cellstissues

Identifiers

PMID25504561
PMCPMC5884688
OpenAlexW2171560520

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.