Evidence map›Paper›PMID 24902740›Full record

ArticleCirculation. Heart failure2014

A bioengineered hydrogel system enables targeted and sustained intramyocardial delivery of neuregulin, activating the cardiomyocyte cell cycle and enhancing ventricular function in a murine model of ischemic cardiomyopathy.

Jeffrey E Cohen, Brendan P Purcell, John W MacArthur, Anbin Mu, Yasuhiro Shudo, Jay B Patel, Christopher M Brusalis, Alen Trubelja, Alexander S Fairman, Bryan B Edwards and 7 more

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

Article in Circulation. Heart failure, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed, 1 pooled it
4.3field-weighted citation impact, top 5% 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

40 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Neuregulin-1β Mitigates Doxorubicin-Induced Cardiotoxicity viaInternational journal of molecular sciences · 2026
    Article
  5. Review
  6. Review
  7. Article
  8. Review
  9. Review
  10. Article
  11. Article
  12. Manipulating Cardiomyocyte Plasticity for Heart Regeneration.Frontiers in cell and developmental biology · 2022
    Review
  13. Review
  14. Review
  15. Review
  16. Navigating the Crossroads of Cell Therapy and Natural Heart Regeneration.Frontiers in cell and developmental biology · 2021
    Review
  17. Article
  18. Review
  19. Review
  20. Article
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

17 authors at 1 institution in 1 country.

Jeffrey E CohenFrom the Department of Cardiothoracic Surgery, Stanford University, CA (J.E.C., J.W.M., Y.S., J.B.P., B.B.E., Y.J.W.); and Departments of Surgery, Division of Cardiovascular Surgery (J.E.C., J.W.M., C.M.B., A.T., A.S.F., G.H., W.H., P.A.), Bioengineering (B.P.P., M.S.D., J.A.B.), and Cardiology (A.M., K.B.M.), University of Pennsylvania, Philadelphia.
Brendan P PurcellFrom the Department of Cardiothoracic Surgery, Stanford University, CA (J.E.C., J.W.M., Y.S., J.B.P., B.B.E., Y.J.W.); and Departments of Surgery, Division of Cardiovascular Surgery (J.E.C., J.W.M., C.M.B., A.T., A.S.F., G.H., W.H., P.A.), Bioengineering (B.P.P., M.S.D., J.A.B.), and Cardiology (A.M., K.B.M.), University of Pennsylvania, Philadelphia.
John W MacArthurFrom the Department of Cardiothoracic Surgery, Stanford University, CA (J.E.C., J.W.M., Y.S., J.B.P., B.B.E., Y.J.W.); and Departments of Surgery, Division of Cardiovascular Surgery (J.E.C., J.W.M., C.M.B., A.T., A.S.F., G.H., W.H., P.A.), Bioengineering (B.P.P., M.S.D., J.A.B.), and Cardiology (A.M., K.B.M.), University of Pennsylvania, Philadelphia.
Anbin MuFrom the Department of Cardiothoracic Surgery, Stanford University, CA (J.E.C., J.W.M., Y.S., J.B.P., B.B.E., Y.J.W.); and Departments of Surgery, Division of Cardiovascular Surgery (J.E.C., J.W.M., C.M.B., A.T., A.S.F., G.H., W.H., P.A.), Bioengineering (B.P.P., M.S.D., J.A.B.), and Cardiology (A.M., K.B.M.), University of Pennsylvania, Philadelphia.
Yasuhiro ShudoFrom the Department of Cardiothoracic Surgery, Stanford University, CA (J.E.C., J.W.M., Y.S., J.B.P., B.B.E., Y.J.W.); and Departments of Surgery, Division of Cardiovascular Surgery (J.E.C., J.W.M., C.M.B., A.T., A.S.F., G.H., W.H., P.A.), Bioengineering (B.P.P., M.S.D., J.A.B.), and Cardiology (A.M., K.B.M.), University of Pennsylvania, Philadelphia.
Jay B PatelFrom the Department of Cardiothoracic Surgery, Stanford University, CA (J.E.C., J.W.M., Y.S., J.B.P., B.B.E., Y.J.W.); and Departments of Surgery, Division of Cardiovascular Surgery (J.E.C., J.W.M., C.M.B., A.T., A.S.F., G.H., W.H., P.A.), Bioengineering (B.P.P., M.S.D., J.A.B.), and Cardiology (A.M., K.B.M.), University of Pennsylvania, Philadelphia.
Christopher M BrusalisFrom the Department of Cardiothoracic Surgery, Stanford University, CA (J.E.C., J.W.M., Y.S., J.B.P., B.B.E., Y.J.W.); and Departments of Surgery, Division of Cardiovascular Surgery (J.E.C., J.W.M., C.M.B., A.T., A.S.F., G.H., W.H., P.A.), Bioengineering (B.P.P., M.S.D., J.A.B.), and Cardiology (A.M., K.B.M.), University of Pennsylvania, Philadelphia.
Alen TrubeljaFrom the Department of Cardiothoracic Surgery, Stanford University, CA (J.E.C., J.W.M., Y.S., J.B.P., B.B.E., Y.J.W.); and Departments of Surgery, Division of Cardiovascular Surgery (J.E.C., J.W.M., C.M.B., A.T., A.S.F., G.H., W.H., P.A.), Bioengineering (B.P.P., M.S.D., J.A.B.), and Cardiology (A.M., K.B.M.), University of Pennsylvania, Philadelphia.
Alexander S FairmanFrom the Department of Cardiothoracic Surgery, Stanford University, CA (J.E.C., J.W.M., Y.S., J.B.P., B.B.E., Y.J.W.); and Departments of Surgery, Division of Cardiovascular Surgery (J.E.C., J.W.M., C.M.B., A.T., A.S.F., G.H., W.H., P.A.), Bioengineering (B.P.P., M.S.D., J.A.B.), and Cardiology (A.M., K.B.M.), University of Pennsylvania, Philadelphia.
Bryan B EdwardsFrom the Department of Cardiothoracic Surgery, Stanford University, CA (J.E.C., J.W.M., Y.S., J.B.P., B.B.E., Y.J.W.); and Departments of Surgery, Division of Cardiovascular Surgery (J.E.C., J.W.M., C.M.B., A.T., A.S.F., G.H., W.H., P.A.), Bioengineering (B.P.P., M.S.D., J.A.B.), and Cardiology (A.M., K.B.M.), University of Pennsylvania, Philadelphia.
Mollie S DavisFrom the Department of Cardiothoracic Surgery, Stanford University, CA (J.E.C., J.W.M., Y.S., J.B.P., B.B.E., Y.J.W.); and Departments of Surgery, Division of Cardiovascular Surgery (J.E.C., J.W.M., C.M.B., A.T., A.S.F., G.H., W.H., P.A.), Bioengineering (B.P.P., M.S.D., J.A.B.), and Cardiology (A.M., K.B.M.), University of Pennsylvania, Philadelphia.
George HungFrom the Department of Cardiothoracic Surgery, Stanford University, CA (J.E.C., J.W.M., Y.S., J.B.P., B.B.E., Y.J.W.); and Departments of Surgery, Division of Cardiovascular Surgery (J.E.C., J.W.M., C.M.B., A.T., A.S.F., G.H., W.H., P.A.), Bioengineering (B.P.P., M.S.D., J.A.B.), and Cardiology (A.M., K.B.M.), University of Pennsylvania, Philadelphia.
William HiesingerFrom the Department of Cardiothoracic Surgery, Stanford University, CA (J.E.C., J.W.M., Y.S., J.B.P., B.B.E., Y.J.W.); and Departments of Surgery, Division of Cardiovascular Surgery (J.E.C., J.W.M., C.M.B., A.T., A.S.F., G.H., W.H., P.A.), Bioengineering (B.P.P., M.S.D., J.A.B.), and Cardiology (A.M., K.B.M.), University of Pennsylvania, Philadelphia.
Pavan AtluriFrom the Department of Cardiothoracic Surgery, Stanford University, CA (J.E.C., J.W.M., Y.S., J.B.P., B.B.E., Y.J.W.); and Departments of Surgery, Division of Cardiovascular Surgery (J.E.C., J.W.M., C.M.B., A.T., A.S.F., G.H., W.H., P.A.), Bioengineering (B.P.P., M.S.D., J.A.B.), and Cardiology (A.M., K.B.M.), University of Pennsylvania, Philadelphia.
Kenneth B MarguliesFrom the Department of Cardiothoracic Surgery, Stanford University, CA (J.E.C., J.W.M., Y.S., J.B.P., B.B.E., Y.J.W.); and Departments of Surgery, Division of Cardiovascular Surgery (J.E.C., J.W.M., C.M.B., A.T., A.S.F., G.H., W.H., P.A.), Bioengineering (B.P.P., M.S.D., J.A.B.), and Cardiology (A.M., K.B.M.), University of Pennsylvania, Philadelphia.
Jason A BurdickFrom the Department of Cardiothoracic Surgery, Stanford University, CA (J.E.C., J.W.M., Y.S., J.B.P., B.B.E., Y.J.W.); and Departments of Surgery, Division of Cardiovascular Surgery (J.E.C., J.W.M., C.M.B., A.T., A.S.F., G.H., W.H., P.A.), Bioengineering (B.P.P., M.S.D., J.A.B.), and Cardiology (A.M., K.B.M.), University of Pennsylvania, Philadelphia.
Y Joseph WooFrom the Department of Cardiothoracic Surgery, Stanford University, CA (J.E.C., J.W.M., Y.S., J.B.P., B.B.E., Y.J.W.); and Departments of Surgery, Division of Cardiovascular Surgery (J.E.C., J.W.M., C.M.B., A.T., A.S.F., G.H., W.H., P.A.), Bioengineering (B.P.P., M.S.D., J.A.B.), and Cardiology (A.M., K.B.M.), University of Pennsylvania, Philadelphia. joswoo@stanford.edu.
Stanford University · US

Funding

ANGIOGENIC TISSUE ENGINEERING TO LIMIT POST-INFARCTION VENTRICULAR REMODELINGR01HL089315 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI WOO, Y JOSEPH · 2008 to 2023
$6.4M
NHLBI NIH HHS R01 HL089315
6 · The paper itself

Abstract

backgroundNeuregulin-1β (NRG) is a member of the epidermal growth factor family possessing a critical role in cardiomyocyte development and proliferation. Systemic administration of NRG demonstrated efficacy in cardiomyopathy animal models, leading to clinical trials using daily NRG infusions. This approach is hindered by requiring daily infusions and off-target exposure. Therefore, this study aimed to encapsulate NRG in a hydrogel to be directly delivered to the myocardium, accomplishing sustained localized NRG delivery. METHODS AND

resultsNRG was encapsulated in hydrogel, and release over 14 days was confirmed by ELISA in vitro. Sprague-Dawley rats were used for cardiomyocyte isolation. Cells were stimulated by PBS, NRG, hydrogel, or NRG-hydrogel (NRG-HG) and evaluated for proliferation. Cardiomyocytes demonstrated EdU (5-ethynyl-2'-deoxyuridine) and phosphorylated histone H3 positivity in the NRG-HG group only. For in vivo studies, 2-month-old mice (n=60) underwent left anterior descending coronary artery ligation and were randomized to the 4 treatment groups mentioned. Only NRG-HG-treated mice demonstrated phosphorylated histone H3 and Ki67 positivity along with decreased caspase-3 activity compared with all controls. NRG was detected in myocardium 6 days after injection without evidence of off-target exposure in NRG-HG animals. At 2 weeks, the NRG-HG group exhibited enhanced left ventricular ejection fraction, decreased left ventricular area, and augmented borderzone thickness.

conclusionsTargeted and sustained delivery of NRG directly to the myocardial borderzone augments cardiomyocyte mitotic activity, decreases apoptosis, and greatly enhances left ventricular function in a model of ischemic cardiomyopathy. This novel approach to NRG administration avoids off-target exposure and represents a clinically translatable strategy in myocardial regenerative therapeutics.

Indexed as

AnimalsAnimals, NewbornBioengineeringCardiomyopathiesCell ProliferationCells, CulturedDelayed-Action PreparationsDisease Models, AnimalHydrogel, Polyethylene Glycol DimethacrylateImmunohistochemistryInjectionsMaleMiceMice, Inbred C57BLMicroscopy, ConfocalMyocardial IschemiaDelayed-Action PreparationsHydrogel, Polyethylene Glycol DimethacrylateNeuregulin-1heart failureischemiamolecular biologymuscle cellsmyocardial infarction

Identifiers

PMID24902740
PMCPMC4157671
OpenAlexW2158274087

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.