Evidence map›Paper›PMID 34762860›Full record

ArticleCell stem cell2022

Hif-1a suppresses ROS-induced proliferation of cardiac fibroblasts following myocardial infarction.

Vaibhao Janbandhu, Vikram Tallapragada, Ralph Patrick, Yanzhen Li, Dhanushi Abeygunawardena, David T Humphreys, Ella M M A Martin, Alexander O Ward, Osvaldo Contreras, Nona Farbehi and 5 more

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

Article in Cell stem cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 122 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
122citing papers in PubMed, 1 pooled it
20.7field-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

122 citing papers in PubMed, 1 synthesis or guideline pooled it, 207 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Review
  5. Article
  6. Function ofInsects · 2026
    Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Function ofInsects · 2026
    Article
  15. Article
  16. Article
  17. Article
  18. Review
  19. Review
  20. Article

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

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

15 authors at 3 institutions in 2 countries.

Vaibhao JanbandhuVictor Chang Cardiac Research Institute, Darlinghurst, NSW, Australia; St. Vincent's Clinical School, UNSW Sydney, NSW, Australia. Electronic address: v.janbandhu@victorchang.edu.au.
Vikram TallapragadaVictor Chang Cardiac Research Institute, Darlinghurst, NSW, Australia; St. Vincent's Clinical School, UNSW Sydney, NSW, Australia.
Ralph PatrickVictor Chang Cardiac Research Institute, Darlinghurst, NSW, Australia; St. Vincent's Clinical School, UNSW Sydney, NSW, Australia.
Yanzhen LiDepartment of Biomedical Engineering, Duke University, Durham, NC 27708, USA.
Dhanushi AbeygunawardenaVictor Chang Cardiac Research Institute, Darlinghurst, NSW, Australia; School of Biotechnology and Biomolecular Science, University of New South Wales, Sydney, NSW, Australia.
David T HumphreysVictor Chang Cardiac Research Institute, Darlinghurst, NSW, Australia; St. Vincent's Clinical School, UNSW Sydney, NSW, Australia.
Ella M M A MartinVictor Chang Cardiac Research Institute, Darlinghurst, NSW, Australia.
Alexander O WardVictor Chang Cardiac Research Institute, Darlinghurst, NSW, Australia; St. Vincent's Clinical School, UNSW Sydney, NSW, Australia.
Osvaldo ContrerasVictor Chang Cardiac Research Institute, Darlinghurst, NSW, Australia; St. Vincent's Clinical School, UNSW Sydney, NSW, Australia.
Nona FarbehiGarvan Weizmann Centre for Cellular Genomics, Garvan Institute of Medical Research Sydney, NSW 2010, Australia.
Ernestene YaoVictor Chang Cardiac Research Institute, Darlinghurst, NSW, Australia.
Junjie DuVictor Chang Cardiac Research Institute, Darlinghurst, NSW, Australia.
Sally L DunwoodieVictor Chang Cardiac Research Institute, Darlinghurst, NSW, Australia; St. Vincent's Clinical School, UNSW Sydney, NSW, Australia.
Nenad BursacDepartment of Biomedical Engineering, Duke University, Durham, NC 27708, USA; Department of Medicine, Duke University, Durham, NC 27708, USA.
Richard P HarveyVictor Chang Cardiac Research Institute, Darlinghurst, NSW, Australia; St. Vincent's Clinical School, UNSW Sydney, NSW, Australia; School of Biotechnology and Biomolecular Science, University of New South Wales, Sydney, NSW, Australia. Electronic address: r.harvey@victorchang.edu.au.
Victor Chang Cardiac Research Institute · AUDuke University · USGarvan Institute of Medical Research · AU

Funding

Integrated Cellular and Tissue Engineering for Ischemic Heart DiseaseU01HL134764 · NHLBI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI BURSAC, NENAD, KAMP, TIMOTHY J. · 2016 to 2022
$7.7M
In Vitro and In Situ Engineering of Fibroblasts for Cardiac RepairR01HL132389 · NHLBI · DUKE UNIVERSITY · PI BURSAC, NENAD · 2016 to 2019
$2.0M
Engineering of Human Excitable Tissues from Unexcitable CellsR01HL126524 · NHLBI · DUKE UNIVERSITY · PI BURSAC, NENAD · 2016 to 2019
$1.9M
NHLBI NIH HHS R01 HL126524NHLBI NIH HHS R01 HL132389NHLBI NIH HHS U01 HL134764
6 · The paper itself

Abstract

We report that cardiac fibroblasts (CFs) and mesenchymal progenitors are more hypoxic than other cardiac interstitial populations, express more hypoxia-inducible factor 1α (HIF-1α), and exhibit increased glycolytic metabolism. CF-specific deletion of Hif-1a resulted in decreased HIF-1 target gene expression and increased mesenchymal progenitors in uninjured hearts and increased CF activation without proliferation following sham injury, as demonstrated using single-cell RNA sequencing (scRNA-seq). After myocardial infarction (MI), however, there was ∼50% increased CF proliferation and excessive scarring and contractile dysfunction, a scenario replicated in 3D engineered cardiac microtissues. CF proliferation was associated with higher reactive oxygen species (ROS) as occurred also in wild-type mice treated with the mitochondrial ROS generator MitoParaquat (MitoPQ). The mitochondrial-targeted antioxidant MitoTEMPO rescued Hif-1a mutant phenotypes. Thus, HIF-1α in CFs provides a critical braking mechanism against excessive post-ischemic CF activation and proliferation through regulation of mitochondrial ROS. CFs are potential cellular targets for designer antioxidant therapies in cardiovascular disease.

Indexed as

Myocardial InfarctionAnimalsAntioxidantsCell ProliferationFibroblastsHypoxia-Inducible Factor 1, alpha SubunitMiceReactive Oxygen SpeciesAntioxidantsHypoxia-Inducible Factor 1, alpha SubunitReactive Oxygen Species3D cardiac microtissuesantioxidant therapiescardiac fibroblastscardiac fibrosisHif-1ahypoxiamesenchymal progenitorsmitochondrial reactive oxygen speciesmyocardial infarctionROSsingle-cell RNA-seq

Identifiers

PMID34762860
PMCPMC9021927
OpenAlexW3214202539

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.