Evidence map›Paper›PMID 24572786›Full record

ArticleGene therapy2014

Effect of bortezomib on the efficacy of AAV9.SERCA2a treatment to preserve cardiac function in a rat pressure-overload model of heart failure.

Antoine H Chaanine, Mathieu Nonnenmacher, Erik Kohlbrenner, Dongzhu Jin, Jason C Kovacic, Fadi G Akar, Roger J Hajjar, Thomas Weber

Open access · bronzeAbstract read
In one paragraph

Article in Gene therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
1.6field-weighted citation impact, top 16% 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

19 citing papers in PubMed, 25 citations in OpenAlex.

  1. Review
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  8. Article
  9. Review
  10. Article
  11. Article
  12. An Observational Study from Long-Term AAV Re-administration in Two Hemophilia Dogs.Molecular therapy. Methods & clinical development · 2018
    Article
  13. Article
  14. Prevention of Atrial Fibrillation by Using Sarcoplasmic Reticulum Calcium ATPase Pump Overexpression in a Rabbit Model of Rapid Atrial Pacing.Medical science monitor : international medical journal of experimental and clinical research · 2017
    Article
  15. Article
  16. AAV9 delivering a modified human Mullerian inhibiting substance as a gene therapy in patient-derived xenografts of ovarian cancer.Proceedings of the National Academy of Sciences of the United States of America · 2015
    Article
  17. Article
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  19. Review
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

8 authors at 1 institution in 1 country.

Antoine H Chaanine *Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, NY 10029.
Mathieu Nonnenmacher *Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, NY 10029.
Erik KohlbrennerCardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, NY 10029.
Dongzhu JinCardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, NY 10029.
Jason C KovacicCardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, NY 10029.
Fadi G AkarCardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, NY 10029.
Roger J HajjarCardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, NY 10029.
Thomas WeberCardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, NY 10029.
Icahn School of Medicine at Mount Sinai · US

Funding

TRAINING PROGRAM IN MOLECULAR AND CELLULAR CARDIOLOGYT32HL007824 · NHLBI · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI GELB, BRUCE D · 1995 to 2022
$8.6M
TRIP: Targeted Gene Therapy for the Treatment of Heart FailureP50HL112324 · NHLBI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI ASCHEIM, DEBORAH DAVIS, HAJJAR, ROGER J. · 2012 to 2014
$6.4M
C-TRIP: Targeted Gene Therapy for the Treatment of Heart Failure (P20)P20HL100396 · NHLBI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI HAJJAR, ROGER J. · 2010 to 2011
$1.7M
Gene Therapy with Cardiotropic Vectors for the Treatment of Heart FailureR01HL088434 · NHLBI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI HAJJAR, ROGER J. · 2010 to 2013
$1.7M
Regression of cardiac hypertrophyR01HL093183 · NHLBI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI HAJJAR, ROGER J. · 2009 to 2010
$1.1M
Cellular and molecular mechanisms of endothelial repair and atherosclerosisK08HL111330 · NHLBI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI KOVACIC, JASON CIRIL · 2012 to 2016
$647k
Integrative Investigation of Mitochondrial DysfunctionR21HL097108 · NHLBI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI AKAR, FADI GABRIEL · 2011 to 2012
$466k
NHLBI NIH HHS HHSN268201000045CNHLBI NIH HHS HL088434NHLBI NIH HHS HL097108NHLBI NIH HHS K08 HL111330NHLBI NIH HHS NIH R01 HL093183NHLBI NIH HHS P20 HL100396NHLBI NIH HHS P50 HL112324NHLBI NIH HHS R01 HL088434NHLBI NIH HHS R01 HL093183NHLBI NIH HHS R21 HL097108NHLBI NIH HHS T32 HL007824
6 · The paper itself

Abstract

Adeno-associated virus (AAV)-based vectors are promising vehicles for therapeutic gene delivery, including for the treatment for heart failure. It has been demonstrated for each of the AAV serotypes 1 through 8 that inhibition of the proteasome results in increased transduction efficiencies. For AAV9, however, the effect of proteasome inhibitors on in vivo transduction has until now not been evaluated. Here we demonstrate, in a well-established rodent heart failure model, that concurrent treatment with the proteasome inhibitor bortezomib does not enhance the efficacy of AAV9.SERCA2a to improve cardiac function as examined by echocardiography and pressure volume analysis. Western blot analysis of SERCA2a protein and reverse transcription-PCR of SERCA2a mRNA demonstrated that bortezomib had no effect on either endogenous rat SERCA2a levels nor on expression levels of human SERCA2a delivered by AAV9.SERCA2a. Similarly, the number of AAV9 genomes in heart samples was unaffected by bortezomib treatment. Interestingly, whereas transduction of HeLa cells and neonatal rat cardiomyocytes by AAV9 was stimulated by bortezomib, transduction of adult rat cardiomyocytes was inhibited. These results indicate an organ/cell-type-specific effect of proteasome inhibition on AAV9 transduction. A future detailed analysis of the underlying molecular mechanisms promises to facilitate the development of improved AAV vectors.

Indexed as

Genetic TherapyAnimalsBoronic AcidsBortezomibDependovirusDisease Models, AnimalGenetic VectorsHeart FailureHumansMyocardiumMyocytes, CardiacPyrazinesRatsSarcoplasmic Reticulum Calcium-Transporting ATPasesBoronic AcidsBortezomibPyrazinesSarcoplasmic Reticulum Calcium-Transporting ATPases

Identifiers

PMID24572786
PMCPMC3976435
OpenAlexW2005754597

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.