Evidence map›Paper›PMID 27834691›Full record

ArticleArteriosclerosis, thrombosis, and vascular biology2017

Zebrafish Model for Functional Screening of Flow-Responsive Genes.

Jovana Serbanovic-Canic, Amalia de Luca, Christina Warboys, Pedro F Ferreira, Le A Luong, Sarah Hsiao, Ismael Gauci, Marwa Mahmoud, Shuang Feng, Celine Souilhol and 11 more

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PubMed Full text at PMC Publisher
In one paragraph

Article in Arteriosclerosis, thrombosis, and vascular biology, 2017. 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
3.0field-weighted citation impact, top 9% 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, 57 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

21 authors at 1 institution in 1 country.

Jovana Serbanovic-CanicFrom the Department of Infection, Immunity and Cardiovascular Disease (J.S.-C., L.A.L., S.H., I.G., M.M., S.F., C.S., N.B., J.-P.A., V.R., T.J.A.C., P.C.E.), INSIGNEO Institute for In Silico Medicine (J.S.-C., V.R., T.J.A.C., P.C.E.), and the Bateson Centre (J.S.-C., J.-P.A., T.J.A.C., P.C.E.), University of Sheffield, United Kingdom; and Departments of Cardiovascular Science (A.d.L., C.W., J.C.M., D.O.H.), Imaging (P.F.F., D.F.), Bioengineering (R.K.), and Aeronautics (S.S.) Imperial College London, United Kingdom; and Cancer Institute, Faculty of Medical Sciences (H.W.), University College London, United Kingdom.
Amalia de LucaFrom the Department of Infection, Immunity and Cardiovascular Disease (J.S.-C., L.A.L., S.H., I.G., M.M., S.F., C.S., N.B., J.-P.A., V.R., T.J.A.C., P.C.E.), INSIGNEO Institute for In Silico Medicine (J.S.-C., V.R., T.J.A.C., P.C.E.), and the Bateson Centre (J.S.-C., J.-P.A., T.J.A.C., P.C.E.), University of Sheffield, United Kingdom; and Departments of Cardiovascular Science (A.d.L., C.W., J.C.M., D.O.H.), Imaging (P.F.F., D.F.), Bioengineering (R.K.), and Aeronautics (S.S.) Imperial College London, United Kingdom; and Cancer Institute, Faculty of Medical Sciences (H.W.), University College London, United Kingdom.
Christina WarboysFrom the Department of Infection, Immunity and Cardiovascular Disease (J.S.-C., L.A.L., S.H., I.G., M.M., S.F., C.S., N.B., J.-P.A., V.R., T.J.A.C., P.C.E.), INSIGNEO Institute for In Silico Medicine (J.S.-C., V.R., T.J.A.C., P.C.E.), and the Bateson Centre (J.S.-C., J.-P.A., T.J.A.C., P.C.E.), University of Sheffield, United Kingdom; and Departments of Cardiovascular Science (A.d.L., C.W., J.C.M., D.O.H.), Imaging (P.F.F., D.F.), Bioengineering (R.K.), and Aeronautics (S.S.) Imperial College London, United Kingdom; and Cancer Institute, Faculty of Medical Sciences (H.W.), University College London, United Kingdom.
Pedro F FerreiraFrom the Department of Infection, Immunity and Cardiovascular Disease (J.S.-C., L.A.L., S.H., I.G., M.M., S.F., C.S., N.B., J.-P.A., V.R., T.J.A.C., P.C.E.), INSIGNEO Institute for In Silico Medicine (J.S.-C., V.R., T.J.A.C., P.C.E.), and the Bateson Centre (J.S.-C., J.-P.A., T.J.A.C., P.C.E.), University of Sheffield, United Kingdom; and Departments of Cardiovascular Science (A.d.L., C.W., J.C.M., D.O.H.), Imaging (P.F.F., D.F.), Bioengineering (R.K.), and Aeronautics (S.S.) Imperial College London, United Kingdom; and Cancer Institute, Faculty of Medical Sciences (H.W.), University College London, United Kingdom.
Le A LuongFrom the Department of Infection, Immunity and Cardiovascular Disease (J.S.-C., L.A.L., S.H., I.G., M.M., S.F., C.S., N.B., J.-P.A., V.R., T.J.A.C., P.C.E.), INSIGNEO Institute for In Silico Medicine (J.S.-C., V.R., T.J.A.C., P.C.E.), and the Bateson Centre (J.S.-C., J.-P.A., T.J.A.C., P.C.E.), University of Sheffield, United Kingdom; and Departments of Cardiovascular Science (A.d.L., C.W., J.C.M., D.O.H.), Imaging (P.F.F., D.F.), Bioengineering (R.K.), and Aeronautics (S.S.) Imperial College London, United Kingdom; and Cancer Institute, Faculty of Medical Sciences (H.W.), University College London, United Kingdom.
Sarah HsiaoFrom the Department of Infection, Immunity and Cardiovascular Disease (J.S.-C., L.A.L., S.H., I.G., M.M., S.F., C.S., N.B., J.-P.A., V.R., T.J.A.C., P.C.E.), INSIGNEO Institute for In Silico Medicine (J.S.-C., V.R., T.J.A.C., P.C.E.), and the Bateson Centre (J.S.-C., J.-P.A., T.J.A.C., P.C.E.), University of Sheffield, United Kingdom; and Departments of Cardiovascular Science (A.d.L., C.W., J.C.M., D.O.H.), Imaging (P.F.F., D.F.), Bioengineering (R.K.), and Aeronautics (S.S.) Imperial College London, United Kingdom; and Cancer Institute, Faculty of Medical Sciences (H.W.), University College London, United Kingdom.
Ismael GauciFrom the Department of Infection, Immunity and Cardiovascular Disease (J.S.-C., L.A.L., S.H., I.G., M.M., S.F., C.S., N.B., J.-P.A., V.R., T.J.A.C., P.C.E.), INSIGNEO Institute for In Silico Medicine (J.S.-C., V.R., T.J.A.C., P.C.E.), and the Bateson Centre (J.S.-C., J.-P.A., T.J.A.C., P.C.E.), University of Sheffield, United Kingdom; and Departments of Cardiovascular Science (A.d.L., C.W., J.C.M., D.O.H.), Imaging (P.F.F., D.F.), Bioengineering (R.K.), and Aeronautics (S.S.) Imperial College London, United Kingdom; and Cancer Institute, Faculty of Medical Sciences (H.W.), University College London, United Kingdom.
Marwa MahmoudFrom the Department of Infection, Immunity and Cardiovascular Disease (J.S.-C., L.A.L., S.H., I.G., M.M., S.F., C.S., N.B., J.-P.A., V.R., T.J.A.C., P.C.E.), INSIGNEO Institute for In Silico Medicine (J.S.-C., V.R., T.J.A.C., P.C.E.), and the Bateson Centre (J.S.-C., J.-P.A., T.J.A.C., P.C.E.), University of Sheffield, United Kingdom; and Departments of Cardiovascular Science (A.d.L., C.W., J.C.M., D.O.H.), Imaging (P.F.F., D.F.), Bioengineering (R.K.), and Aeronautics (S.S.) Imperial College London, United Kingdom; and Cancer Institute, Faculty of Medical Sciences (H.W.), University College London, United Kingdom.
Shuang FengFrom the Department of Infection, Immunity and Cardiovascular Disease (J.S.-C., L.A.L., S.H., I.G., M.M., S.F., C.S., N.B., J.-P.A., V.R., T.J.A.C., P.C.E.), INSIGNEO Institute for In Silico Medicine (J.S.-C., V.R., T.J.A.C., P.C.E.), and the Bateson Centre (J.S.-C., J.-P.A., T.J.A.C., P.C.E.), University of Sheffield, United Kingdom; and Departments of Cardiovascular Science (A.d.L., C.W., J.C.M., D.O.H.), Imaging (P.F.F., D.F.), Bioengineering (R.K.), and Aeronautics (S.S.) Imperial College London, United Kingdom; and Cancer Institute, Faculty of Medical Sciences (H.W.), University College London, United Kingdom.
Celine SouilholFrom the Department of Infection, Immunity and Cardiovascular Disease (J.S.-C., L.A.L., S.H., I.G., M.M., S.F., C.S., N.B., J.-P.A., V.R., T.J.A.C., P.C.E.), INSIGNEO Institute for In Silico Medicine (J.S.-C., V.R., T.J.A.C., P.C.E.), and the Bateson Centre (J.S.-C., J.-P.A., T.J.A.C., P.C.E.), University of Sheffield, United Kingdom; and Departments of Cardiovascular Science (A.d.L., C.W., J.C.M., D.O.H.), Imaging (P.F.F., D.F.), Bioengineering (R.K.), and Aeronautics (S.S.) Imperial College London, United Kingdom; and Cancer Institute, Faculty of Medical Sciences (H.W.), University College London, United Kingdom.
Neil BowdenFrom the Department of Infection, Immunity and Cardiovascular Disease (J.S.-C., L.A.L., S.H., I.G., M.M., S.F., C.S., N.B., J.-P.A., V.R., T.J.A.C., P.C.E.), INSIGNEO Institute for In Silico Medicine (J.S.-C., V.R., T.J.A.C., P.C.E.), and the Bateson Centre (J.S.-C., J.-P.A., T.J.A.C., P.C.E.), University of Sheffield, United Kingdom; and Departments of Cardiovascular Science (A.d.L., C.W., J.C.M., D.O.H.), Imaging (P.F.F., D.F.), Bioengineering (R.K.), and Aeronautics (S.S.) Imperial College London, United Kingdom; and Cancer Institute, Faculty of Medical Sciences (H.W.), University College London, United Kingdom.
John-Paul AshtonFrom the Department of Infection, Immunity and Cardiovascular Disease (J.S.-C., L.A.L., S.H., I.G., M.M., S.F., C.S., N.B., J.-P.A., V.R., T.J.A.C., P.C.E.), INSIGNEO Institute for In Silico Medicine (J.S.-C., V.R., T.J.A.C., P.C.E.), and the Bateson Centre (J.S.-C., J.-P.A., T.J.A.C., P.C.E.), University of Sheffield, United Kingdom; and Departments of Cardiovascular Science (A.d.L., C.W., J.C.M., D.O.H.), Imaging (P.F.F., D.F.), Bioengineering (R.K.), and Aeronautics (S.S.) Imperial College London, United Kingdom; and Cancer Institute, Faculty of Medical Sciences (H.W.), University College London, United Kingdom.
Henning WalczakFrom the Department of Infection, Immunity and Cardiovascular Disease (J.S.-C., L.A.L., S.H., I.G., M.M., S.F., C.S., N.B., J.-P.A., V.R., T.J.A.C., P.C.E.), INSIGNEO Institute for In Silico Medicine (J.S.-C., V.R., T.J.A.C., P.C.E.), and the Bateson Centre (J.S.-C., J.-P.A., T.J.A.C., P.C.E.), University of Sheffield, United Kingdom; and Departments of Cardiovascular Science (A.d.L., C.W., J.C.M., D.O.H.), Imaging (P.F.F., D.F.), Bioengineering (R.K.), and Aeronautics (S.S.) Imperial College London, United Kingdom; and Cancer Institute, Faculty of Medical Sciences (H.W.), University College London, United Kingdom.
David FirminFrom the Department of Infection, Immunity and Cardiovascular Disease (J.S.-C., L.A.L., S.H., I.G., M.M., S.F., C.S., N.B., J.-P.A., V.R., T.J.A.C., P.C.E.), INSIGNEO Institute for In Silico Medicine (J.S.-C., V.R., T.J.A.C., P.C.E.), and the Bateson Centre (J.S.-C., J.-P.A., T.J.A.C., P.C.E.), University of Sheffield, United Kingdom; and Departments of Cardiovascular Science (A.d.L., C.W., J.C.M., D.O.H.), Imaging (P.F.F., D.F.), Bioengineering (R.K.), and Aeronautics (S.S.) Imperial College London, United Kingdom; and Cancer Institute, Faculty of Medical Sciences (H.W.), University College London, United Kingdom.
Rob KramsFrom the Department of Infection, Immunity and Cardiovascular Disease (J.S.-C., L.A.L., S.H., I.G., M.M., S.F., C.S., N.B., J.-P.A., V.R., T.J.A.C., P.C.E.), INSIGNEO Institute for In Silico Medicine (J.S.-C., V.R., T.J.A.C., P.C.E.), and the Bateson Centre (J.S.-C., J.-P.A., T.J.A.C., P.C.E.), University of Sheffield, United Kingdom; and Departments of Cardiovascular Science (A.d.L., C.W., J.C.M., D.O.H.), Imaging (P.F.F., D.F.), Bioengineering (R.K.), and Aeronautics (S.S.) Imperial College London, United Kingdom; and Cancer Institute, Faculty of Medical Sciences (H.W.), University College London, United Kingdom.
Justin C MasonFrom the Department of Infection, Immunity and Cardiovascular Disease (J.S.-C., L.A.L., S.H., I.G., M.M., S.F., C.S., N.B., J.-P.A., V.R., T.J.A.C., P.C.E.), INSIGNEO Institute for In Silico Medicine (J.S.-C., V.R., T.J.A.C., P.C.E.), and the Bateson Centre (J.S.-C., J.-P.A., T.J.A.C., P.C.E.), University of Sheffield, United Kingdom; and Departments of Cardiovascular Science (A.d.L., C.W., J.C.M., D.O.H.), Imaging (P.F.F., D.F.), Bioengineering (R.K.), and Aeronautics (S.S.) Imperial College London, United Kingdom; and Cancer Institute, Faculty of Medical Sciences (H.W.), University College London, United Kingdom.
Dorian O HaskardFrom the Department of Infection, Immunity and Cardiovascular Disease (J.S.-C., L.A.L., S.H., I.G., M.M., S.F., C.S., N.B., J.-P.A., V.R., T.J.A.C., P.C.E.), INSIGNEO Institute for In Silico Medicine (J.S.-C., V.R., T.J.A.C., P.C.E.), and the Bateson Centre (J.S.-C., J.-P.A., T.J.A.C., P.C.E.), University of Sheffield, United Kingdom; and Departments of Cardiovascular Science (A.d.L., C.W., J.C.M., D.O.H.), Imaging (P.F.F., D.F.), Bioengineering (R.K.), and Aeronautics (S.S.) Imperial College London, United Kingdom; and Cancer Institute, Faculty of Medical Sciences (H.W.), University College London, United Kingdom.
Spencer SherwinFrom the Department of Infection, Immunity and Cardiovascular Disease (J.S.-C., L.A.L., S.H., I.G., M.M., S.F., C.S., N.B., J.-P.A., V.R., T.J.A.C., P.C.E.), INSIGNEO Institute for In Silico Medicine (J.S.-C., V.R., T.J.A.C., P.C.E.), and the Bateson Centre (J.S.-C., J.-P.A., T.J.A.C., P.C.E.), University of Sheffield, United Kingdom; and Departments of Cardiovascular Science (A.d.L., C.W., J.C.M., D.O.H.), Imaging (P.F.F., D.F.), Bioengineering (R.K.), and Aeronautics (S.S.) Imperial College London, United Kingdom; and Cancer Institute, Faculty of Medical Sciences (H.W.), University College London, United Kingdom.
Victoria RidgerFrom the Department of Infection, Immunity and Cardiovascular Disease (J.S.-C., L.A.L., S.H., I.G., M.M., S.F., C.S., N.B., J.-P.A., V.R., T.J.A.C., P.C.E.), INSIGNEO Institute for In Silico Medicine (J.S.-C., V.R., T.J.A.C., P.C.E.), and the Bateson Centre (J.S.-C., J.-P.A., T.J.A.C., P.C.E.), University of Sheffield, United Kingdom; and Departments of Cardiovascular Science (A.d.L., C.W., J.C.M., D.O.H.), Imaging (P.F.F., D.F.), Bioengineering (R.K.), and Aeronautics (S.S.) Imperial College London, United Kingdom; and Cancer Institute, Faculty of Medical Sciences (H.W.), University College London, United Kingdom.
Timothy J A ChicoFrom the Department of Infection, Immunity and Cardiovascular Disease (J.S.-C., L.A.L., S.H., I.G., M.M., S.F., C.S., N.B., J.-P.A., V.R., T.J.A.C., P.C.E.), INSIGNEO Institute for In Silico Medicine (J.S.-C., V.R., T.J.A.C., P.C.E.), and the Bateson Centre (J.S.-C., J.-P.A., T.J.A.C., P.C.E.), University of Sheffield, United Kingdom; and Departments of Cardiovascular Science (A.d.L., C.W., J.C.M., D.O.H.), Imaging (P.F.F., D.F.), Bioengineering (R.K.), and Aeronautics (S.S.) Imperial College London, United Kingdom; and Cancer Institute, Faculty of Medical Sciences (H.W.), University College London, United Kingdom.
Paul C EvansFrom the Department of Infection, Immunity and Cardiovascular Disease (J.S.-C., L.A.L., S.H., I.G., M.M., S.F., C.S., N.B., J.-P.A., V.R., T.J.A.C., P.C.E.), INSIGNEO Institute for In Silico Medicine (J.S.-C., V.R., T.J.A.C., P.C.E.), and the Bateson Centre (J.S.-C., J.-P.A., T.J.A.C., P.C.E.), University of Sheffield, United Kingdom; and Departments of Cardiovascular Science (A.d.L., C.W., J.C.M., D.O.H.), Imaging (P.F.F., D.F.), Bioengineering (R.K.), and Aeronautics (S.S.) Imperial College London, United Kingdom; and Cancer Institute, Faculty of Medical Sciences (H.W.), University College London, United Kingdom. paul.evans@sheffield.ac.uk.
Imperial College London · GB

Funding

British Heart Foundation FS/13/27/30191British Heart Foundation PG/09/088/28058British Heart Foundation PG/13/2/29902British Heart Foundation PG/15/17/31332British Heart Foundation PG/15/49/31595British Heart Foundation RG/11/13/29055British Heart Foundation RG/13/1/30042
6 · The paper itself

Abstract

objectiveAtherosclerosis is initiated at branches and bends of arteries exposed to disturbed blood flow that generates low shear stress. This mechanical environment promotes lesions by inducing endothelial cell (EC) apoptosis and dysfunction via mechanisms that are incompletely understood. Although transcriptome-based studies have identified multiple shear-responsive genes, most of them have an unknown function. To address this, we investigated whether zebrafish embryos can be used for functional screening of mechanosensitive genes that regulate EC apoptosis in mammalian arteries. APPROACH AND

resultsFirst, we demonstrated that flow regulates EC apoptosis in developing zebrafish vasculature. Specifically, suppression of blood flow in zebrafish embryos (by targeting cardiac troponin) enhanced that rate of EC apoptosis (≈10%) compared with controls exposed to flow (≈1%). A panel of candidate regulators of apoptosis were identified by transcriptome profiling of ECs from high and low shear stress regions of the porcine aorta. Genes that displayed the greatest differential expression and possessed 1 to 2 zebrafish orthologues were screened for the regulation of apoptosis in zebrafish vasculature exposed to flow or no-flow conditions using a knockdown approach. A phenotypic change was observed in 4 genes; p53-related protein (PERP) and programmed cell death 2-like protein functioned as positive regulators of apoptosis, whereas angiopoietin-like 4 and cadherin 13 were negative regulators. The regulation of perp, cdh13, angptl4, and pdcd2l by shear stress and the effects of perp and cdh13 on EC apoptosis were confirmed by studies of cultured EC exposed to flow.

conclusionsWe conclude that a zebrafish model of flow manipulation coupled to gene knockdown can be used for functional screening of mechanosensitive genes in vascular ECs, thus providing potential therapeutic targets to prevent or treat endothelial injury at atheroprone sites.

Indexed as

ApoptosisGene Expression Regulation, DevelopmentalAnimalsAnimals, Genetically ModifiedAtherosclerosisCells, CulturedEmbryo, NonmammalianEndothelial CellsFemaleGene Expression ProfilingGene Knockdown TechniquesGene Regulatory NetworksGenetic Association StudiesGenetic Predisposition to DiseaseHumansMechanotransduction, CellularZebrafish Proteinsapoptosisatherosclerosisendothelial cellsshear stressZebrafish

Identifiers

PMID27834691
PMCPMC5172514
OpenAlexW2564606133

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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.