Evidence map›Paper›PMID 21723687›Full record

ArticleJournal of vascular surgery2011

Adeno-associated virus serotype 9-mediated overexpression of extracellular superoxide dismutase improves recovery from surgical hind-limb ischemia in BALB/c mice.

Amina Saqib, Konkal-Matt R Prasad, Arabindra B Katwal, John M Sanders, R John Lye, Brent A French, Brian H Annex

Abstract read
In one paragraph

Article in Journal of vascular surgery, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
0.8field-weighted citation impact, top 26% 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

16 citing papers in PubMed, 22 citations in OpenAlex.

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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

7 authors at 1 institution in 1 country.

Amina SaqibDivision of Cardiovascular Medicine/Department of Medicine, University of Virginia, Charlottesville, VA 22908, USA.
Konkal-Matt R Prasad
Arabindra B Katwal
John M Sanders
R John Lye
Brent A French
Brian H Annex
University of Virginia · US

Funding

Systems Biology of Angiogenesis: from Molecules to TherapyR33HL088286 · NHLBI · UNIVERSITY OF VIRGINIA · PI ANNEX, BRIAN H · 2006 to 2008
$1.2M
GENE THERAPY FOR MYOCARDIAL STUNNING AND INFARCTIONR01HL058582 · NHLBI · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI FRENCH, BRENT A · 1997 to 2006
$872k
NHLBI NIH HHS R01 HL058582NHLBI NIH HHS R33 HL088286
6 · The paper itself

Abstract

objectiveNeovascularization is a physiologic repair process that partly depends on nitric oxide. Extracellular superoxide dismutase (EcSOD) is the major scavenger of superoxide. It is an important regulator of nitric oxide bioavailability and thus protects against vascular dysfunction. We hypothesized that overexpression of EcSOD in skeletal muscle would improve recovery from hind-limb ischemia.

methodsAdeno-associated virus serotype 9 (AAV9) vectors expressing EcSOD or luciferase (control) from the cytomegalovirus promoter were cross-packaged into AAV9 capsids and injected intramuscularly into the hind-limb muscles (1 × 10(11) viral genomes/limb) of 12-week-old mice. Ischemia was induced after intramuscular injections. Laser Doppler was used to measure limb perfusion on days 0, 7, and 14 after injection. Values were expressed as a ratio relative to the nonischemic limb. EcSOD expression was measured by Western blotting. Capillary density was documented by immunohistochemical staining for platelet endothelial cell adhesion molecule. Apoptosis was assessed by terminal deoxynucleotide transferase-mediated biotin-deoxy uridine triphosphate nick-end labeling and necrosis was visually evaluated daily.

resultsEcSOD expression was twofold upregulated in EcSOD treated vs control ischemic muscles at day 14. Capillary density (capillaries/fiber) was 1.9-fold higher in treated (1.65 ± 0.02) vs control muscle (0.78 ± 0.17, P < .05). Recovery of perfusion ratio at day 14 after ischemia was 1.5-fold greater in EcSOD vs control mice (P < .05). The percentage of apoptotic nuclei was 1.3% ± 0.4% in EcSOD-treated mice compared with 4.2% ± 0.2% in controls (P < .001). Limb necrosis was also significantly lower in EcSOD vs control mice.

conclusionAAV9-mediated overexpression of EcSOD in skeletal muscle significantly improves recovery from hind-limb ischemia in mice, consistent with improved capillary density and perfusion ratios in treated mice.

Indexed as

Genetic TherapyGenetic VectorsNeovascularization, PhysiologicAnimalsApoptosisBlotting, WesternCapillariesCyclic GMPDependovirusDisease Models, AnimalHindlimbImmunohistochemistryInjections, IntramuscularIn Situ Nick-End LabelingIschemiaLaser-Doppler FlowmetryCyclic GMPLuciferases, FireflyPlatelet Endothelial Cell Adhesion Molecule-1Recombinant Fusion ProteinsSod3 protein, mouseSuperoxide Dismutase

Identifiers

PMID21723687
PMCPMC3166979
OpenAlexW2082137186

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Registered trials

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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.