Evidence map›Paper›PMID 32686471›Full record

ArticleCirculation2020

Attenuation of Oxidative Injury With Targeted Expression of NADPH Oxidase 2 Short Hairpin RNA Prevents Onset and Maintenance of Electrical Remodeling in the Canine Atrium: A Novel Gene Therapy Approach to Atrial Fibrillation.

Shin Yoo, Anna Pfenniger, Jacob Hoffman, Wenwei Zhang, Jason Ng, Amy Burrell, David A Johnson, Georg Gussak, Trent Waugh, Suzanne Bull and 6 more

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

Article in Circulation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
3.1field-weighted citation impact, top 7% 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

32 citing papers in PubMed, 36 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Review
  5. Review
  6. Gene Therapies in Atrial Fibrillation.Journal of cardiovascular translational research · 2025
    Review
  7. Article
  8. Oxidative stress and atrial fibrillation.Journal of molecular and cellular cardiology · 2024
    Review
  9. Gene therapy for atrial fibrillation.Journal of molecular and cellular cardiology · 2024
    Review
  10. Review
  11. Review
  12. Modulation of NOX2 causes obesity-mediated atrial fibrillation.The Journal of clinical investigation · 2024
    Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. Review
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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

16 authors at 2 institutions in 1 country.

Shin Yoo *Feinberg Cardiovascular and Renal Research Institute, Northwestern University Feinberg School of Medicine, Chicago, IL (S.Y., A.P., J.H., W.Z., J.N., A.B., D.A.J., G.G., T.W., S.B., B.B., B.P.K., R.P., J.A.W., R.A.).
Anna Pfenniger *Feinberg Cardiovascular and Renal Research Institute, Northwestern University Feinberg School of Medicine, Chicago, IL (S.Y., A.P., J.H., W.Z., J.N., A.B., D.A.J., G.G., T.W., S.B., B.B., B.P.K., R.P., J.A.W., R.A.).
Jacob HoffmanFeinberg Cardiovascular and Renal Research Institute, Northwestern University Feinberg School of Medicine, Chicago, IL (S.Y., A.P., J.H., W.Z., J.N., A.B., D.A.J., G.G., T.W., S.B., B.B., B.P.K., R.P., J.A.W., R.A.).
Wenwei ZhangFeinberg Cardiovascular and Renal Research Institute, Northwestern University Feinberg School of Medicine, Chicago, IL (S.Y., A.P., J.H., W.Z., J.N., A.B., D.A.J., G.G., T.W., S.B., B.B., B.P.K., R.P., J.A.W., R.A.).
Jason NgFeinberg Cardiovascular and Renal Research Institute, Northwestern University Feinberg School of Medicine, Chicago, IL (S.Y., A.P., J.H., W.Z., J.N., A.B., D.A.J., G.G., T.W., S.B., B.B., B.P.K., R.P., J.A.W., R.A.).
Amy BurrellFeinberg Cardiovascular and Renal Research Institute, Northwestern University Feinberg School of Medicine, Chicago, IL (S.Y., A.P., J.H., W.Z., J.N., A.B., D.A.J., G.G., T.W., S.B., B.B., B.P.K., R.P., J.A.W., R.A.).
David A JohnsonFeinberg Cardiovascular and Renal Research Institute, Northwestern University Feinberg School of Medicine, Chicago, IL (S.Y., A.P., J.H., W.Z., J.N., A.B., D.A.J., G.G., T.W., S.B., B.B., B.P.K., R.P., J.A.W., R.A.).
Georg GussakFeinberg Cardiovascular and Renal Research Institute, Northwestern University Feinberg School of Medicine, Chicago, IL (S.Y., A.P., J.H., W.Z., J.N., A.B., D.A.J., G.G., T.W., S.B., B.B., B.P.K., R.P., J.A.W., R.A.).
Trent WaughFeinberg Cardiovascular and Renal Research Institute, Northwestern University Feinberg School of Medicine, Chicago, IL (S.Y., A.P., J.H., W.Z., J.N., A.B., D.A.J., G.G., T.W., S.B., B.B., B.P.K., R.P., J.A.W., R.A.).
Suzanne BullFeinberg Cardiovascular and Renal Research Institute, Northwestern University Feinberg School of Medicine, Chicago, IL (S.Y., A.P., J.H., W.Z., J.N., A.B., D.A.J., G.G., T.W., S.B., B.B., B.P.K., R.P., J.A.W., R.A.).
Brandon BenefieldFeinberg Cardiovascular and Renal Research Institute, Northwestern University Feinberg School of Medicine, Chicago, IL (S.Y., A.P., J.H., W.Z., J.N., A.B., D.A.J., G.G., T.W., S.B., B.B., B.P.K., R.P., J.A.W., R.A.).
Bradley P KnightFeinberg Cardiovascular and Renal Research Institute, Northwestern University Feinberg School of Medicine, Chicago, IL (S.Y., A.P., J.H., W.Z., J.N., A.B., D.A.J., G.G., T.W., S.B., B.B., B.P.K., R.P., J.A.W., R.A.).
Rod PassmanFeinberg Cardiovascular and Renal Research Institute, Northwestern University Feinberg School of Medicine, Chicago, IL (S.Y., A.P., J.H., W.Z., J.N., A.B., D.A.J., G.G., T.W., S.B., B.B., B.P.K., R.P., J.A.W., R.A.).
J Andrew WasserstromFeinberg Cardiovascular and Renal Research Institute, Northwestern University Feinberg School of Medicine, Chicago, IL (S.Y., A.P., J.H., W.Z., J.N., A.B., D.A.J., G.G., T.W., S.B., B.B., B.P.K., R.P., J.A.W., R.A.).
Gary L AistrupMasonic Medical Research Institute, Utica, NY (G.L.A.).
Rishi AroraFeinberg Cardiovascular and Renal Research Institute, Northwestern University Feinberg School of Medicine, Chicago, IL (S.Y., A.P., J.H., W.Z., J.N., A.B., D.A.J., G.G., T.W., S.B., B.B., B.P.K., R.P., J.A.W., R.A.).
Northwestern University · USMasonic Medical Research Laboratory · US

Funding

Atrial arrhythmias and Ca2+ waves in HF: simulation and experimental studiesR01HL119095 · NHLBI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI SHIFERAW, YOHANNES, WASSERSTROM, JOHN ANDREW · 2014 to 2018
$3.0M
Disruption of Autonomic Pathways in the Left Atrium by Inhibition of G-proteinsR01HL093490 · NHLBI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI ARORA, RISHI · 2009 to 2013
$2.5M
Pathophysiological Significance of Atrial Fibrillation Electrogram PatternsR01HL125881 · NHLBI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI ARORA, RISHI · 2015 to 2019
$2.4M
Oxidative stress contributes to atrial fibrillation by causing remodeling of the autonomic nervous systemR01HL140061 · NHLBI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI ARORA, RISHI · 2018 to 2021
$2.3M
NHLBI NIH HHS R01 HL093490NHLBI NIH HHS R01 HL119095NHLBI NIH HHS R01 HL125881NHLBI NIH HHS R01 HL140061
6 · The paper itself

Abstract

backgroundAtrial fibrillation (AF) is the most common heart rhythm disorder in adults and a major cause of stroke. Unfortunately, current treatments of AF are suboptimal because they are not targeted to the molecular mechanisms underlying AF. Using a highly novel gene therapy approach in a canine, rapid atrial pacing model of AF, we demonstrate that NADPH oxidase 2 (NOX2) generated oxidative injury causes upregulation of a constitutively active form of acetylcholine-dependent K

methodsTo understand the mechanism by which oxidative injury promotes the genesis and maintenance of AF, we performed targeted injection of NOX2 short hairpin RNA (followed by electroporation to facilitate gene delivery) in atria of healthy dogs followed by rapid atrial pacing. We used in vivo high-density electric mapping, isolation of atrial myocytes, whole-cell patch clamping, in vitro tachypacing of atrial myocytes, lucigenin chemiluminescence assay, immunoblotting, real-time polymerase chain reaction, immunohistochemistry, and Masson trichrome staining.

resultsFirst, we demonstrate that generation of oxidative injury in atrial myocytes is a frequency-dependent process, with rapid pacing in canine atrial myocytes inducing oxidative injury through the induction of NOX2 and the generation of mitochondrial reactive oxygen species. We show that oxidative injury likely contributes to electric remodeling in AF by upregulating

conclusionsNOX2 oxidative injury (1) underlies the onset, and the maintenance of electric remodeling in AF, as well, and (2) can be successfully prevented with a novel, gene-based approach. Future optimization of this approach may lead to a novel, mechanism-guided therapy for AF.

Indexed as

Atrial FibrillationAtrial RemodelingGene Expression Regulation, EnzymologicGenetic TherapyNADPH Oxidase 2RNA, Small InterferingAnimalsDogsHeart AtriaNADPH Oxidase 2RNA, Small Interferingatrial fibrillationgene therapyIKHNADPH oxidase 2

Identifiers

PMID32686471
PMCPMC9277750
OpenAlexW3089861369

What OpenQuestion holds

Textmetadata
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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.