Evidence map›Paper›PMID 18378570›Full record

ArticleInvestigative ophthalmology & visual science2008

Role of NADPH oxidase and Stat3 in statin-mediated protection against diabetic retinopathy.

Mohamed Al-Shabrawey, Manuela Bartoli, Azza B El-Remessy, Guochuan Ma, Suraporn Matragoon, Tahira Lemtalsi, R William Caldwell, Ruth B Caldwell

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

Article in Investigative ophthalmology & visual science, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers.

0numbers the graph read from it
0cells of the map it votes in
86citing papers in PubMed
4.2field-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

86 citing papers in PubMed, 158 citations in OpenAlex.

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  16. Cellular targets in diabetic retinopathy therapy.World journal of diabetes · 2021
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26 more citing papers are in PubMed but not listed here.

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 2 institutions in 1 country.

Mohamed Al-ShabraweyVascular Biology Center, Medical College of Georgia, Augusta, Georgia 30912-2500, USA.
Manuela Bartoli
Azza B El-Remessy
Guochuan Ma
Suraporn Matragoon
Tahira Lemtalsi
R William Caldwell
Ruth B Caldwell
Augusta University · USCenter for Vascular Biology Research · US

Funding

CELLULAR MECHANISMS OF RETINAL ANGIOGENESISR01EY011766 · MEDICAL COLLEGE OF GEORGIA (MCG) · 1998 to 2005
$1.5M
BLOOD/RETINAL BARRIER CHANGES IN RETINOPATHYR01EY004618 · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · 1985 to 2004
$1.2M
Endothelial Cell Dysfunction in Oxidative Stress ModelsR01HL070215 · MEDICAL COLLEGE OF GEORGIA (MCG) · 2002 to 2005
$1.0M
NEI NIH HHS R01 EY004618NEI NIH HHS R01 EY011766NEI NIH HHS R01 EY04618NEI NIH HHS R01 EY11766NHLBI NIH HHS R01 HL070215NHLBI NIH HHS R01 HL70215
6 · The paper itself

Abstract

purposeInhibitors of 3-hydroxy-3-methylglutaryl CoA reductase (statins) reduce signs of diabetic retinopathy in diabetic patients and animals. Indirect clinical evidence supports the actions of statins in improving cardiovascular function, but the mechanisms of their protective actions in the retina are not understood. Prior studies have implicated oxidative stress and NADPH oxidase-mediated activation of signal transducer and activator of transcription 3 (STAT3) in diabetes-induced increases in expression of vascular endothelial growth factor (VEGF) and intercellular adhesion molecule (ICAM)-1 and breakdown of the blood-retinal barrier (BRB). Because statins are known to be potent antioxidants, the hypothesis for the current study was that the protective effects of statins in preventing diabetic retinopathy involve blockade of diabetes-induced activation of NADPH oxidase and STAT3.

methodsThe hypothesis was tested by experiments in which rats with streptozotocin (STZ)-induced diabetes and retinal endothelial cells maintained in high-glucose medium were treated with simvastatin. Blood-retinal barrier (BRB) function was assayed by determining extravasation of albumin. Oxidative stress was assayed by measuring lipid peroxidation, protein nitration of tyrosine, dihydroethidine oxidation, and chemiluminescence. Immunoprobe techniques were used to determine the levels of NADPH oxidase subunit expression and STAT3 activation.

resultsThese studies showed that simvastatin blocks diabetes or high-glucose-induced increases in VEGF and ICAM-1 and preserves the BRB by a process involving blockade of diabetes/high-glucose-induced activation of STAT3 and NADPH oxidase. Statin treatment also prevents diabetes-induced increases in expression of the NADPH oxidase catalytic and subunit NOX2.

conclusionsThese results suggest that simvastatin protects against the early signs of diabetic retinopathy by preventing NADPH oxidase-mediated activation of STAT3.

Indexed as

AnimalsBlood-Retinal BarrierCattleCells, CulturedDiabetes Mellitus, ExperimentalDiabetic RetinopathyDose-Response Relationship, DrugEndothelial CellsGlucoseHydroxymethylglutaryl-CoA Reductase InhibitorsIntercellular Adhesion Molecule-1MaleMembrane GlycoproteinsNADPH Oxidase 2NADPH OxidasesRatsCybb protein, ratGlucoseHydroxymethylglutaryl-CoA Reductase InhibitorsIntercellular Adhesion Molecule-1Membrane GlycoproteinsNADPH Oxidase 2NADPH OxidasesSimvastatinSTAT3 Transcription FactorVascular Endothelial Growth Factor A

Identifiers

PMID18378570
PMCPMC2819293
OpenAlexW2064710522

What Socratic holds

Textmetadata
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 Socratic graph.