Evidence map›Paper›PMID 26034042›Full record

ArticleCirculation research2015

Mechanosensitive PPAP2B Regulates Endothelial Responses to Atherorelevant Hemodynamic Forces.

Congqing Wu, Ru-Ting Huang, Cheng-Hsiang Kuo, Sandeep Kumar, Chan Woo Kim, Yen-Chen Lin, Yen-Ju Chen, Anna Birukova, Konstantin G Birukov, Nickolai O Dulin and 7 more

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

Article in Circulation research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.

0numbers the graph read from it
0cells of the map it votes in
56citing papers in PubMed
5.6field-weighted citation impact, top 3% 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

56 citing papers in PubMed, 97 citations in OpenAlex.

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  15. FTO-dependent mNature communications · 2023
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  16. Review
  17. MicroRNAs in Mechanical Homeostasis.Cold Spring Harbor perspectives in medicine · 2022
    Review
  18. Review
  19. Targeted polyelectrolyte complex micelles treat vascular complications in vivo.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors at 6 institutions in 2 countries.

Congqing Wu *Department of Medicine, University of Chicago, Los Angeles.
Ru-Ting Huang *Department of Medicine, University of Chicago, Los Angeles.
Cheng-Hsiang KuoDepartment of Medicine, University of Chicago, Los Angeles.
Sandeep KumarDepartment of Biomedical Engineering, Georgia Institute of Technology and Emory University, Los Angeles.
Chan Woo KimDepartment of Biomedical Engineering, Georgia Institute of Technology and Emory University, Los Angeles.
Yen-Chen LinDepartment of Medicine, University of Chicago, Los Angeles.
Yen-Ju ChenDepartment of Medicine, University of Chicago, Los Angeles.
Anna BirukovaDepartment of Medicine, University of Chicago, Los Angeles.
Konstantin G BirukovDepartment of Medicine, University of Chicago, Los Angeles.
Nickolai O DulinDepartment of Medicine, University of Chicago, Los Angeles.
Mete CivelekDepartment of Medicine, University of California, Los Angeles.
Aldons J LusisDepartment of Medicine, University of California, Los Angeles.
Xavier LoyerParis-Cardiovascular Research Center, University Paris Descartes.
Alain TedguiParis-Cardiovascular Research Center, University Paris Descartes.
Guohao DaiDepartment of Biomedical Engineering, Rensselaer Polytechnic Institute.
Hanjoong JoDepartment of Biomedical Engineering, Georgia Institute of Technology and Emory University, Los Angeles.
Yun FangDepartment of Medicine, University of Chicago, Los Angeles.
Emory University · USParis Cardiovascular Research Center · FRRensselaer Polytechnic Institute · USUniversité Paris Cité · FRUniversity of California, Los Angeles · USGeorgia Institute of Technology · US

Funding

T cell triggering events and hypertensionP01HL095070 · NHLBI · EMORY UNIVERSITY · PI LASSEGUE, BERNARD · 2009 to 2019
$20.5M
Control of Lung Permeability by Oxidized PhospholipidsR01HL076259 · NHLBI · UNIVERSITY OF MARYLAND BALTIMORE · PI BIRUKOV, KONSTANTIN · 2004 to 2023
$6.8M
Shear stress, endothelial miRNAs, and AV calcificationR01HL119798 · NHLBI · EMORY UNIVERSITY · PI JO, HANJOONG, YOGANATHAN, AJIT P · 2013 to 2022
$4.7M
Image-based analysis of miRNA deliveryR01HL124879 · NHLBI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI FERRARA, KATHERINE W, JO, HANJOONG · 2014 to 2017
$3.1M
Systems genetics analysis of cardiometabolic trait loci in humans R00HL121172 · NHLBI · UNIVERSITY OF VIRGINIA · PI CIVELEK, METE · 2016 to 2018
$741k
miR-10a regulation of regional arterial endothelial phenotypes in atherosclerosisR00HL103789 · NHLBI · UNIVERSITY OF CHICAGO · PI FANG, YUN · 2013 to 2015
$729k
Systems genetics analysis of cardiometabolic trait loci in humans K99HL121172 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI CIVELEK, METE · 2014 to 2015
$247k
NHLBI NIH HHS K99 HL121172NHLBI NIH HHS K99HL121172NHLBI NIH HHS P01 HL095070NHLBI NIH HHS R00 HL103789NHLBI NIH HHS R00 HL121172NHLBI NIH HHS R01 HL076259NHLBI NIH HHS R01 HL119798NHLBI NIH HHS R01 HL124879
6 · The paper itself

Abstract

rationalePhosPhatidic Acid Phosphatase type 2B (PPAP2B), an integral membrane protein known as lipid phosphate phosphatase (LPP3) that inactivates lysophosphatidic acid, was implicated in coronary artery disease (CAD) by genome-wide association studies. However, it is unclear whether genome-wide association studies-identified coronary artery disease genes, including PPAP2B, participate in mechanotransduction mechanisms by which vascular endothelia respond to local atherorelevant hemodynamics that contribute to the regional nature of atherosclerosis.

objectiveTo establish the critical role of PPAP2B in endothelial responses to hemodynamics. METHODS AND

resultsReduced PPAP2B was detected in vivo in mouse and swine aortic arch (AA) endothelia exposed to chronic disturbed flow, and in mouse carotid artery endothelia subjected to surgically induced acute disturbed flow. In humans, PPAP2B was reduced in the downstream part of carotid plaques where low shear stress prevails. In culture, reduced PPAP2B was measured in human aortic endothelial cells under atherosusceptible waveform mimicking flow in human carotid sinus. Flow-sensitive microRNA-92a and transcription factor KLF2 were identified as upstream inhibitor and activator of endothelial PPAP2B, respectively. PPAP2B suppression abrogated atheroprotection of unidirectional flow; inhibition of lysophosphatidic acid receptor 1 restored the flow-dependent, anti-inflammatory phenotype in PPAP2B-deficient cells. PPAP2B inhibition resulted in myosin light-chain phosphorylation and intercellular gaps, which were abolished by lysophosphatidic acid receptor 1/2 inhibition. Expression quantitative trait locus mapping demonstrated PPAP2B coronary artery disease risk allele is not linked to PPAP2B expression in various human tissues but significantly associated with reduced PPAP2B in human aortic endothelial cells.

conclusionsAtherorelevant flows dynamically modulate endothelial PPAP2B expression through miR-92a and KLF2. Mechanosensitive PPAP2B plays a critical role in promoting anti-inflammatory phenotype and maintaining vascular integrity of endothelial monolayer under atheroprotective flow.

Indexed as

HemodynamicsMechanotransduction, Cellular3' Untranslated RegionsAnimalsAorta, ThoracicAtherosclerosisBinding SitesCells, CulturedEndothelial CellsGene Expression Regulation, EnzymologicGene FrequencyGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansKruppel-Like Transcription FactorsMice3' Untranslated RegionsKLF2 protein, humanKruppel-Like Transcription FactorsMicroRNAsMIRN92 microRNA, humanMyosin Light ChainsPhosphatidate PhosphatasePLPP3 protein, humanPlpp3 protein, mouseReceptors, Lysophosphatidic Acidatherosclerosisendothelial cellsgenome wide association studyhemodynamicsmicroRNAspermeability

Identifiers

PMID26034042
PMCPMC4522239
OpenAlexW2169413839

What OpenQuestion holds

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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.