Evidence map›Paper›PMID 31219556›Full record

ArticleEuropean heart journal2019

Modelling diastolic dysfunction in induced pluripotent stem cell-derived cardiomyocytes from hypertrophic cardiomyopathy patients.

Haodi Wu, Huaxiao Yang, June-Wha Rhee, Joe Z Zhang, Chi Keung Lam, Karim Sallam, Alex C Y Chang, Ning Ma, Jaecheol Lee, Hao Zhang and 3 more

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

Article in European heart journal, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
79citing papers in PubMed, 1 pooled it
12.1field-weighted citation impact, top 1% 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

79 citing papers in PubMed, 1 synthesis or guideline pooled it, 135 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Article
  5. Article
  6. Review
  7. Hypertrophic Cardiomyopathy: Current Perspectives.Reviews in cardiovascular medicine · 2025
    Review
  8. Review
  9. Article
  10. Review
  11. Article
  12. Review
  13. Review
  14. Review
  15. Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Incomplete-penetrant hypertrophic cardiomyopathyProceedings of the National Academy of Sciences of the United States of America · 2024
    Article

19 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 2 institutions in 1 country.

Haodi WuStanford Cardiovascular Institute, Stanford University School of Medicine, 265 Campus Drive, Stanford, CA, USA.
Huaxiao YangStanford Cardiovascular Institute, Stanford University School of Medicine, 265 Campus Drive, Stanford, CA, USA.
June-Wha RheeStanford Cardiovascular Institute, Stanford University School of Medicine, 265 Campus Drive, Stanford, CA, USA.
Joe Z ZhangStanford Cardiovascular Institute, Stanford University School of Medicine, 265 Campus Drive, Stanford, CA, USA.
Chi Keung LamStanford Cardiovascular Institute, Stanford University School of Medicine, 265 Campus Drive, Stanford, CA, USA.
Karim SallamStanford Cardiovascular Institute, Stanford University School of Medicine, 265 Campus Drive, Stanford, CA, USA.
Alex C Y ChangStanford Cardiovascular Institute, Stanford University School of Medicine, 265 Campus Drive, Stanford, CA, USA.
Ning MaStanford Cardiovascular Institute, Stanford University School of Medicine, 265 Campus Drive, Stanford, CA, USA.
Jaecheol LeeStanford Cardiovascular Institute, Stanford University School of Medicine, 265 Campus Drive, Stanford, CA, USA.
Hao ZhangStanford Cardiovascular Institute, Stanford University School of Medicine, 265 Campus Drive, Stanford, CA, USA.
Helen M BlauStanford Cardiovascular Institute, Stanford University School of Medicine, 265 Campus Drive, Stanford, CA, USA.
Donald M BersDepartment of Pharmacology, University of California, 451 Health Sciences Drive, Davis, CA, USA.
Joseph C WuStanford Cardiovascular Institute, Stanford University School of Medicine, 265 Campus Drive, Stanford, CA, USA.
Cardiovascular Institute of the South · USUniversity of California, Davis · US

Funding

Project 3 (Mercola)P01HL141084 · NHLBI · STANFORD UNIVERSITY · PI MARK MERCOLA · 2019 to 2026
$21.1M
Pathophysiological Regulation of Cardiac Myocyte RyR ChannelR01HL092097 · NHLBI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI Donald M Bers, Robyn T Rebbeck · 2010 to 2026
$9.3M
Elucidating Mechanism of Cardiac Fibrosis with Cell Village of Pooled Human iPSCsR01HL130020 · NHLBI · STANFORD UNIVERSITY · PI Ronglih Liao, MARK MERCOLA · 2016 to 2026
$7.3M
Human Induced Pluripotent Stem Cells for Cardiovascular Disease ModelingR01HL113006 · NHLBI · STANFORD UNIVERSITY · PI WU, JOSEPH C. · 2012 to 2025
$6.8M
VECTOR COREP30NS069375 · NINDS · STANFORD UNIVERSITY · PI SHAMLOO, MEHRDAD · 2011 to 2019
$6.3M
Human iPSCs for Elucidating Intercellular Crosstalk Signaling in Dilated CardiomyopathyR01HL141371 · NHLBI · STANFORD UNIVERSITY · PI WONG, WING H., WU, JOSEPH C. · 2018 to 2025
$6.2M
Genome Editing of Human iPSCs to Study Inherited Hypertrophic CardiomyopathyR01HL126527 · NHLBI · STANFORD UNIVERSITY · PI QI, LEI STANLEY, WU, JOSEPH C. · 2015 to 2022
$5.4M
Telomere extension using nucleoside-modified mRNA and exosomes as a novel therapeR01AR063963 · NIAMS · STANFORD UNIVERSITY · PI BLAU, HELEN M · 2012 to 2016
$4.3M
IONIC CONTROL OF CARDIAC MUSCLE CONTRACTION: EC COUPLINGR01HL030077 · NHLBI · UNIVERSITY OF CALIFORNIA RIVERSIDE · PI BERS, DONALD M · 1986 to 2018
$3.8M
High-Throughput Screens to Discover Novel Inhibitors of Leaky RyR2 for Heart Failure TherapyR01HL138539 · NHLBI · UNIVERSITY OF MINNESOTA · PI BERS, DONALD M, CORNEA, RAZVAN LIVIU · 2018 to 2021
$3.1M
A Systems Biology Approach to Study Cardiac Arrhythmias: iPS Cells and In Silico ModelingR01HL128170 · NHLBI · STANFORD UNIVERSITY · PI ALTMAN, RUSS BIAGIO, CLANCY, COLLEEN E · 2015 to 2018
$3.0M
Epigenetic regulation of PDE signaling in dilated cardiomyopathyR00HL133473 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI WU, HAODI · 2021 to 2023
$747k
American Heart Association-American Stroke Association 18POST34030106NHLBI NIH HHS F32 HL134221NHLBI NIH HHS K99 HL133473NHLBI NIH HHS P01 HL141084NHLBI NIH HHS R00 HL133473NHLBI NIH HHS R01 HL030077NHLBI NIH HHS R01 HL092097NHLBI NIH HHS R01 HL113006NHLBI NIH HHS R01 HL126527NHLBI NIH HHS R01 HL128170NHLBI NIH HHS R01 HL130020NHLBI NIH HHS R01 HL138539NHLBI NIH HHS R01 HL141371NIAMS NIH HHS R01 AR063963NINDS NIH HHS P30 NS069375
6 · The paper itself

Abstract

aimsDiastolic dysfunction (DD) is common among hypertrophic cardiomyopathy (HCM) patients, causing major morbidity and mortality. However, its cellular mechanisms are not fully understood, and presently there is no effective treatment. Patient-specific induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) hold great potential for investigating the mechanisms underlying DD in HCM and as a platform for drug discovery. METHODS AND

resultsIn the present study, beating iPSC-CMs were generated from healthy controls and HCM patients with DD. Micropatterned iPSC-CMs from HCM patients showed impaired diastolic function, as evidenced by prolonged relaxation time, decreased relaxation rate, and shortened diastolic sarcomere length. Ratiometric Ca2+ imaging indicated elevated diastolic [Ca2+]i and abnormal Ca2+ handling in HCM iPSC-CMs, which were exacerbated by β-adrenergic challenge. Combining Ca2+ imaging and traction force microscopy, we observed enhanced myofilament Ca2+ sensitivity (measured as dF/Δ[Ca2+]i) in HCM iPSC-CMs. These results were confirmed with genome-edited isogenic iPSC lines that carry HCM mutations, indicating that cytosolic diastolic Ca2+ overload, slowed [Ca2+]i recycling, and increased myofilament Ca2+ sensitivity, collectively impairing the relaxation of HCM iPSC-CMs. Treatment with partial blockade of Ca2+ or late Na+ current reset diastolic Ca2+ homeostasis, restored diastolic function, and improved long-term survival, suggesting that disturbed Ca2+ signalling is an important cellular pathological mechanism of DD. Further investigation showed increased expression of L-type Ca2+channel (LTCC) and transient receptor potential cation channels (TRPC) in HCM iPSC-CMs compared with control iPSC-CMs, which likely contributed to diastolic [Ca2+]i overload.

conclusionIn summary, this study recapitulated DD in HCM at the single-cell level, and revealed novel cellular mechanisms and potential therapeutic targets of DD using iPSC-CMs.

Indexed as

CalciumCardiac MyosinsCardiomyopathy, HypertrophicCarrier ProteinsCase-Control StudiesCell DifferentiationHeart Failure, DiastolicHumansInduced Pluripotent Stem CellsMutationMyocytes, CardiacMyosin Binding Protein CMyosin Heavy ChainsPhenotypeSarcomeresTroponin TCalciumCardiac MyosinsCarrier ProteinsMYH7 protein, humanMyosin Binding Protein CMyosin Heavy ChainsTNNT2 protein, humanTroponin TCalcium homeostasisCardiomyocytesDiastolic dysfunctionHypertrophic cardiomyopathyInduced pluripotent stem cellsMYBPC3MYH7TNNT2

Identifiers

PMID31219556
PMCPMC7963137
OpenAlexW2950717932

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.