Evidence map›Paper›PMID 31082397›Full record

ArticleJournal of molecular and cellular cardiology2019

Targeting HIF-1α in combination with PPARα activation and postnatal factors promotes the metabolic maturation of human induced pluripotent stem cell-derived cardiomyocytes.

Cinsley Gentillon, Dong Li, Meixue Duan, Wen-Mei Yu, Marcela K Preininger, Rajneesh Jha, Antonio Rampoldi, Anita Saraf, Gregory C Gibson, Cheng-Kui Qu and 2 more

Open access · greenAbstract read
In one paragraph

Article in Journal of molecular and cellular cardiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
53citing papers in PubMed, 2 pooled it
8.0field-weighted citation impact, top 2% 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

53 citing papers in PubMed, 2 syntheses or guidelines pooled it, 68 citations in OpenAlex.

  1. Engineering the maturation of stem cell-derived cardiomyocytes.Frontiers in bioengineering and biotechnology · 2023
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  11. The molecular mechanisms of cardiac development and related diseases.Signal transduction and targeted therapy · 2024
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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

12 authors at 2 institutions in 1 country.

Cinsley GentillonDepartment of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA, USA.
Dong LiDepartment of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA, USA.
Meixue DuanSchool of Biological Sciences, Georgia Institute of Technology, Atlanta, GA, USA.
Wen-Mei YuDepartment of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA, USA.
Marcela K PreiningerDepartment of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA, USA; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA.
Rajneesh JhaDepartment of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA, USA.
Antonio RampoldiDepartment of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA, USA.
Anita SarafDepartment of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA, USA.
Gregory C GibsonSchool of Biological Sciences, Georgia Institute of Technology, Atlanta, GA, USA.
Cheng-Kui QuDepartment of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA, USA.
Lou Ann BrownDepartment of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA, USA.
Chunhui XuDepartment of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA, USA; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA. Electronic address: chunhui.xu@emory.edu.
Emory University · USGeorgia Institute of Technology · US

Funding

Maturation of Human Pluripotent Stem Cell-Derived CardiomyocytesR01HL136345 · NHLBI · EMORY UNIVERSITY · PI XU, CHUNHUI · 2018 to 2021
$1.6M
NHLBI NIH HHS R01 HL136345
6 · The paper itself

Abstract

Immature phenotypes of cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) limit the utility of these cells in clinical application and basic research. During cardiac development, postnatal cardiomyocytes experience high oxygen tension along with a concomitant downregulation of hypoxia-inducible factor 1α (HIF-1α), leading to increased fatty acid oxidation (FAO). We hypothesized that targeting HIF-1α alone or in combination with other metabolic regulators could promote the metabolic maturation of hiPSC-CMs. We examined the effect of HIF-1α inhibition on the maturation of hiPSC-CMs and investigated a multipronged approach to promote hiPSC-CM maturation by combining HIF-1α inhibition with molecules that target key pathways involved in the energy metabolism. Cardiac spheres of highly-enriched hiPSC-CMs were treated with a HIF-1α inhibitor alone or in combination with an agonist of peroxisome proliferator activated receptor α (PPARα) and three postnatal factors (triiodothyronine hormone T3, insulin-like growth factor-1 and dexamethasone). HIF-1α inhibition significantly increased FAO and basal and maximal respiration of hiPSC-CMs. Combining HIF-1α inhibition with PPARα activation and the postnatal factors further increased FAO and improved mitochondrial maturation in hiPSC-CMs. Compared with mock-treated cultures, the cultures treated with the five factors had increased mitochondrial content and contained more cells with mitochondrial distribution throughout the cells, which are features of more mature cardiomyocytes. Consistent with these observations, a number of transcriptional regulators of mitochondrial metabolic processes were upregulated in hiPSC-CMs treated with the five factors. Furthermore, these cells had significantly increased Ca

Indexed as

Drug SynergismAnti-Inflammatory AgentsBenzamidesCalciumCell DifferentiationCells, CulturedDexamethasoneEnergy MetabolismFatty AcidsHumansHypoxia-Inducible Factor 1, alpha SubunitInduced Pluripotent Stem CellsInsulin-Like Growth Factor ILipid MetabolismMitochondriaMyocytes, CardiacAnti-Inflammatory AgentsBenzamidesCalciumDexamethasoneFatty AcidsFM19G11HIF1A protein, humanHypoxia-Inducible Factor 1, alpha SubunitInsulin-Like Growth Factor IPPAR alphaTriiodothyronineCalcium transientsCardiomyocyteFatty acidMetabolismStem cell

Identifiers

PMID31082397
PMCPMC6683286
OpenAlexW2944179239

What OpenQuestion holds

Textmetadata
LicenceTDM
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.