Evidence map›Paper›PMID 23846495›Full record

ArticleArteriosclerosis, thrombosis, and vascular biology2013

Cyclophilin A is required for angiotensin II-induced p47phox translocation to caveolae in vascular smooth muscle cells.

Nwe Nwe Soe, Mark Sowden, Padmamalini Baskaran, Elaine M Smolock, Yeonghwan Kim, Patrizia Nigro, Bradford C Berk

Open access · bronzeAbstract read
In one paragraph

Article in Arteriosclerosis, thrombosis, and vascular biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
2.5field-weighted citation impact, top 10% 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

18 citing papers in PubMed, 41 citations in OpenAlex.

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  16. Redox regulation of vascular remodeling.Cellular and molecular life sciences : CMLS · 2016
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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.

Nwe Nwe SoeDepartment of Medicine, Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
Mark Sowden
Padmamalini Baskaran
Elaine M Smolock
Yeonghwan Kim
Patrizia Nigro
Bradford C Berk
University of Wyoming · US

Funding

Oxidative Stress and Vascular Smoth Muscle Cell GrowthR01HL049192 · NHLBI · UNIVERSITY OF WASHINGTON · PI BERK, BRADFORD C · 1995 to 2019
$6.1M
NHLBI NIH HHS HL49192NHLBI NIH HHS R01 HL049192
6 · The paper itself

Abstract

objectiveAngiotensin II (AngII) signal transduction in vascular smooth muscle cells (VSMC) is mediated by reactive oxygen species (ROS). Cyclophilin A (CyPA) is a ubiquitously expressed cytosolic protein that possesses peptidyl-prolyl cis-trans isomerase activity, scaffold function, and significantly enhances AngII-induced ROS production in VSMC. We hypothesized that CyPA regulates AngII-induced ROS generation by promoting translocation of NADPH oxidase cytosolic subunit p47phox to caveolae of the plasma membrane. APPROACH AND

resultsOverexpression of CyPA in CyPA-deficient VSMC (CyPA(-/-)VSMC) significantly increased AngII-stimulated ROS production. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitors (VAS2870 or diphenylene iodonium) significantly attenuated AngII-induced ROS production in CyPA and p47phox-overexpressing CyPA(-/-)VSMC. Cell fractionation and sucrose gradient analyses showed that AngII-induced p47phox plasma membrane translocation, specifically to the caveolae, was reduced in CyPA(-/-)VSMC compared with wild-type-VSMC. Immunofluorescence studies demonstrated that AngII increased p47phox and CyPA colocalization and translocation to the plasma membrane. In addition, immunoprecipitation of CyPA followed by immunoblotting of p47phox and actin showed that AngII increased CyPA and p47phox interaction. AngII-induced p47phox and actin cell cytoskeleton association was attenuated in CyPA(-/-)VSMC. Mechanistically, inhibition of p47phox phosphorylation and phox homology domain deletion attenuated CyPA and p47phox interaction. Finally, cyclosporine A and CyPA-peptidyl-prolyl cis-trans isomerase mutant, R55A, inhibited AngII-stimulated CyPA and p47phox association in VSMC, suggesting that peptidyl-prolyl cis-trans isomerase activity was required for their interaction.

conclusionsThese findings provide the mechanism by which CyPA is an important regulator for AngII-induced ROS generation in VSMC through interaction with p47phox and cell cytoskeleton, which enhances the translocation of p47phox to caveolae.

Indexed as

Actin CytoskeletonAngiotensin IIAnimalsBlotting, WesternCaveolaeCyclophilin ADose-Response Relationship, DrugEnzyme InhibitorsFluorescent Antibody TechniqueHeLa CellsHumansImmunoprecipitationMiceMice, KnockoutMice, TransgenicMicroscopy, FluorescenceAngiotensin IICyclophilin AEnzyme InhibitorsFLAG peptideNADPH Oxidasesneutrophil cytosolic factor 1OligopeptidesPeptidesReactive Oxygen SpeciesReceptor, Angiotensin, Type 1Recombinant Fusion Proteinsangiotensin IIcyclophilin Acytoskeletonp47phox protein, mousereactive oxygen species

Identifiers

PMID23846495
PMCPMC3817838
OpenAlexW2147881867

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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.