Evidence map›Paper›PMID 23316332›Full record

ArticleJournal of the American Heart Association2012

In vivo cardiac cellular reprogramming efficacy is enhanced by angiogenic preconditioning of the infarcted myocardium with vascular endothelial growth factor.

Megumi Mathison, Robert P Gersch, Ahmed Nasser, Sarit Lilo, Mallory Korman, Mitchell Fourman, Neil Hackett, Kenneth Shroyer, Jianchang Yang, Yupo Ma and 2 more

Open access · goldAbstract readComparative Study
In one paragraph

Article in Journal of the American Heart Association, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
82citing papers in PubMed, 1 pooled it
12.0field-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

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

  1. Pooled it
  2. Review
  3. Frontiers in cell and developmental biology · 2026
    Article
  4. Article
  5. Review
  6. Advances in fibroblast-based cardiac reprogramming in the treatment of heart disease.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025
    Review
  7. Review
  8. Review
  9. Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Fibroblast Reprogramming in Cardiac Repair.JACC. Basic to translational science · 2024
    Review
  15. Review
  16. Direct cardiac reprogramming: A new technology for cardiac repair.Journal of molecular and cellular cardiology · 2023
    Review
  17. Review
  18. Translational perspectives on cardiac reprogramming.Seminars in cell & developmental biology · 2022
    Review
  19. Article
  20. Review

22 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

12 authors at 2 institutions in 1 country.

Megumi MathisonDepartment of Surgery, Stony Brook University Medical Center, Stony Brook, NY, USA.
Robert P Gersch
Ahmed Nasser
Sarit Lilo
Mallory Korman
Mitchell Fourman
Neil Hackett
Kenneth Shroyer
Jianchang Yang
Yupo Ma
Ronald G Crystal
Todd K Rosengart
Stony Brook University Hospital · USCornell University · US

Funding

NHLBI NIH HHS 5R01HL0855095-05
6 · The paper itself

Abstract

backgroundIn situ cellular reprogramming offers the possibility of regenerating functional cardiomyocytes directly from scar fibroblasts, obviating the challenges of cell implantation. We hypothesized that pretreating scar with gene transfer of the angiogenic vascular endothelial growth factor (VEGF) would enhance the efficacy of this strategy. METHODS AND

resultsGata4, Mef2c, and Tbx5 (GMT) administration via lentiviral transduction was demonstrated to transdifferentiate rat fibroblasts into (induced) cardiomyocytes in vitro by cardiomyocyte marker studies. Fisher 344 rats underwent coronary ligation and intramyocardial administration of an adenovirus encoding all 3 major isoforms of VEGF (AdVEGF-All6A(+)) or an AdNull control vector (n=12/group). Lentivirus encoding GMT or a GFP control was administered to each animal 3 weeks later, followed by histologic and echocardiographic analyses. GMT administration reduced the extent of fibrosis by half compared with GFP controls (12 ± 2% vs 24 ± 3%, P<0.01) and reduced the number of myofibroblasts detected in the infarct zone by 4-fold. GMT-treated animals also demonstrated greater density of cardiomyocyte-specific marker beta myosin heavy chain 7(+) cells compared with animals receiving GFP with or without VEGF (P<0.01). Ejection fraction was significantly improved after GMT vs GFP administration (12 ± 3% vs -7 ± 3%, P<0.01). Eight (73%) GFP animals but no GMT animals demonstrated decreased ejection fraction during this interval (P<0.01). Also, improvement in ejection fraction was 4-fold greater in GMT/VEGF vs GMT/null animals (17 ± 2% vs 4 ± 1%, P<0.05).

conclusionsVEGF administration to infarcted myocardium enhances the efficacy of GMT-mediated cellular reprogramming in improving myocardial function and reducing the extent of myocardial fibrosis compared with the use of GMT or VEGF alone.

Indexed as

AnimalsDrug Therapy, CombinationEchocardiographyFibrosisFluorescent Antibody TechniqueGATA4 Transcription FactorGene Transfer TechniquesMEF2 Transcription FactorsMyocardial InfarctionMyocytes, CardiacMyogenic Regulatory FactorsNeovascularization, PhysiologicRatsRats, Inbred F344T-Box Domain ProteinsTranscription FactorsGATA4 Transcription FactorMEF2C protein, ratMEF2 Transcription FactorsMyogenic Regulatory FactorsT-Box Domain ProteinsT-box transcription factor 5Transcription FactorsVascular Endothelial Growth Factor Aangiogenesisgene therapymyocardial infarctionstem cells

Identifiers

PMID23316332
PMCPMC3540681
OpenAlexW2149469368

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.