Evidence map›Paper›PMID 23065925›Full record

ArticleThe journal of gene medicine

Adeno-associated virus serotype 9 administered systemically after reperfusion preferentially targets cardiomyocytes in the infarct border zone with pharmacodynamics suitable for the attenuation of left ventricular remodeling.

Prasad R Konkalmatt, Feng Wang, Bryan A Piras, Yaqin Xu, Daniel M O'Connor, Ronald J Beyers, Frederick H Epstein, Brian H Annex, John A Hossack, Brent A French

Abstract read
In one paragraph

Article in The journal of gene medicine. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.1field-weighted citation impact, top 20% 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

13 citing papers in PubMed, 25 citations in OpenAlex.

  1. Unifying and unique roles of non-coding RNA biomarkers in liver and heart fibrosis.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2026
    Review
  2. Article
  3. Article
  4. Article
  5. CITED4 gene therapy protects against maladaptive cardiac remodeling after ischemia/reperfusion injury in mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2024
    Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. 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

10 authors at 1 institution in 1 country.

Prasad R KonkalmattDepartment of Biomedical Engineering, University of Virginia, Charlottesville, VA, USA.
Feng Wang
Bryan A Piras
Yaqin Xu
Daniel M O'Connor
Ronald J Beyers
Frederick H Epstein
Brian H Annex
John A Hossack
Brent A French
University of Virginia · US

Funding

QUANTITATIVE 3D ULTRASOUND IMAGING OF THE MURINE HEARTR01EB001826 · NIBIB · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI HOSSACK, JOHN A · 2003 to 2012
$2.4M
Inflammation and Oxidative Stress in Hyperglycemic Exacerbation of Infarct SizeR01HL092305 · NHLBI · UNIVERSITY OF VIRGINIA · PI FRENCH, BRENT A, KRON, IRVING L. · 2009 to 2013
$1.9M
GENE THERAPY FOR MYOCARDIAL STUNNING AND INFARCTIONR01HL058582 · NHLBI · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI FRENCH, BRENT A · 1997 to 2006
$872k
VisualSonics Vevo 2100 Small Animal Ultrasound Imaging System and AccessoriesS10RR027333 · NCRR · UNIVERSITY OF VIRGINIA · PI HOSSACK, JOHN A · 2010 to 2010
$482k
NCRR NIH HHS S10 RR027333NHLBI NIH HHS HL092305NHLBI NIH HHS R01 HL058582NHLBI NIH HHS R01 HL092305NHLBI NIH HHS R01S HL058582NIBIB NIH HHS R01 EB001826
6 · The paper itself

Abstract

backgroundAdeno-associated virus serotype 9 (AAV9) vectors provide efficient and uniform gene expression to normal myocardium following systemic administration, with kinetics that approach steady-state within 2-3 weeks. However, as a result of the delayed onset of gene expression, AAV vectors have not previously been administered intravenously after reperfusion for post-infarct gene therapy applications. The present study evaluated the therapeutic potential of post-myocardial infarction gene delivery using intravenous AAV9.

methodsAAV9 vectors expressing firefly luciferase, enhanced green fluorescent protein (eGFP) or extracellular superoxide dismutase genes from the cardiac troponin-T (cTnT) promoter (AcTnTLuc, AcTnTeGFP, AcTnTEcSOD) were employed. AcTnTLuc was administered intravenously at 10 min and at 1, 2 and 3 days post-ischemia/reperfusion (IR), and the kinetics of luciferase expression were assessed with bioluminescence imaging. AcTnTeGFP was used to evaluate the distribution of eGFP expression. High-resolution echocardiography was used to evaluate the effects of AcTnTEcSOD on left ventricular (LV) remodeling when injected 10 min post-IR.

resultsCompared to sham animals, luciferase expression at 2 days after vector administration was elevated by four-, 24-, 210- and 213-fold in groups injected at 10 min, 1 day, 2 days and 3 days post-IR, respectively. The expression of cTnT-driven eGFP was strongest in cardiomyocytes bordering the infarct zone. In the efficacy study of EcSOD, post-infarct LV end-systolic and end-diastolic volumes at days 14 and 28 were significantly smaller in the EcSOD group compared to the control.

conclusionsSystemic administration of AAV9 vectors after IR both elevates and accelerates gene expression that preferentially targets cardiomyocytes in the border zone with pharmacodynamics suitable for the attenuation of LV remodeling.

Indexed as

Myocardial ReperfusionAnimalsDependovirusGene ExpressionGenetic TherapyGenetic VectorsGreen Fluorescent ProteinsLuciferasesMiceMice, Inbred C57BLMyocardial InfarctionMyocardial IschemiaMyocardial Reperfusion InjuryMyocytes, CardiacReference ValuesTransgenesenhanced green fluorescent proteinGreen Fluorescent ProteinsLuciferases

Identifiers

PMID23065925
PMCPMC3729029
OpenAlexW1871421695

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.