Evidence map›Paper›PMID 29051139›Full record

ArticleArteriosclerosis, thrombosis, and vascular biology2018

Mining the Stiffness-Sensitive Transcriptome in Human Vascular Smooth Muscle Cells Identifies Long Noncoding RNA Stiffness Regulators.

Christopher K Yu, Tina Xu, Richard K Assoian, Daniel J Rader

Abstract read
In one paragraph

Article in Arteriosclerosis, thrombosis, and vascular biology, 2018. 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
–field-weighted citation impact
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.

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  5. Heterogeneous expression of alternatively spliced lncRNA mediates vascular smooth cell plasticity.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  6. Elastin, arterial mechanics, and stenosis.American journal of physiology. Cell physiology · 2022
    Review
  7. Review
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  9. Article
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  12. lncRNA-PACER upregulatesGastroenterology report · 2021
    Article
  13. Review
  14. Article
  15. Article
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  18. Article
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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

4 authors.

Christopher K YuFrom the Perelman School of Medicine (C.K.Y.), Department of Systems Pharmacology and Translational Therapeutics (T.X., R.K.A.), Program in Translational Biomechanics, Institute of Translational Medicine and Therapeutics (T.X., R.K.A.), and Departments of Genetics, Medicine, and Pediatrics, Perelman School of Medicine (D.J.R.), University of Pennsylvania, Philadelphia.
Tina XuFrom the Perelman School of Medicine (C.K.Y.), Department of Systems Pharmacology and Translational Therapeutics (T.X., R.K.A.), Program in Translational Biomechanics, Institute of Translational Medicine and Therapeutics (T.X., R.K.A.), and Departments of Genetics, Medicine, and Pediatrics, Perelman School of Medicine (D.J.R.), University of Pennsylvania, Philadelphia.
Richard K AssoianFrom the Perelman School of Medicine (C.K.Y.), Department of Systems Pharmacology and Translational Therapeutics (T.X., R.K.A.), Program in Translational Biomechanics, Institute of Translational Medicine and Therapeutics (T.X., R.K.A.), and Departments of Genetics, Medicine, and Pediatrics, Perelman School of Medicine (D.J.R.), University of Pennsylvania, Philadelphia.
Daniel J RaderFrom the Perelman School of Medicine (C.K.Y.), Department of Systems Pharmacology and Translational Therapeutics (T.X., R.K.A.), Program in Translational Biomechanics, Institute of Translational Medicine and Therapeutics (T.X., R.K.A.), and Departments of Genetics, Medicine, and Pediatrics, Perelman School of Medicine (D.J.R.), University of Pennsylvania, Philadelphia. rader@pennmedicine.upenn.edu.

Funding

Multidisciplinary Training in Cardiovascular BiologyT32HL007954 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI DAVIES, PETER FRANCIS · 2000 to 2019
$9.9M
apoE, arterial biomechanics, and cardiovascular diseaseR01HL119346 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI ASSOIAN, RICHARD · 2014 to 2017
$1.8M
NHLBI NIH HHS R01 HL119346NHLBI NIH HHS T32 HL007954
6 · The paper itself

Abstract

objectiveVascular extracellular matrix stiffening is a risk factor for aortic and coronary artery disease. How matrix stiffening regulates the transcriptome profile of human aortic and coronary vascular smooth muscle cells (VSMCs) is not well understood. Furthermore, the role of long noncoding RNAs (lncRNAs) in the cellular response to stiffening has never been explored. This study characterizes the stiffness-sensitive (SS) transcriptome of human aortic and coronary VSMCs and identifies potential key lncRNA regulators of stiffness-dependent VSMC functions. APPROACH AND

resultsAortic and coronary VSMCs were cultured on hydrogel substrates mimicking physiological and pathological extracellular matrix stiffness. Total RNAseq was performed to compare the SS transcriptome profiles of aortic and coronary VSMCs. We identified 3098 genes (2842 protein coding and 157 lncRNA) that were stiffness sensitive in both aortic and coronary VSMCs (false discovery rate <1%). Hierarchical clustering revealed that aortic and coronary VSMCs grouped by stiffness rather than cell origin. Conservation analyses also revealed that SS genes were more conserved than stiffness-insensitive genes. These VSMC SS genes were less tissue-type specific and expressed in more tissues than stiffness-insensitive genes. Using unbiased systems analyses, we identified MALAT1 as an SS lncRNA that regulates stiffness-dependent VSMC proliferation and migration in vitro and in vivo.

conclusionsThis study provides the transcriptomic landscape of human aortic and coronary VSMCs in response to extracellular matrix stiffness and identifies novel SS human lncRNAs. Our data suggest that the SS transcriptome is evolutionarily important to VSMCs function and that SS lncRNAs can act as regulators of stiffness-dependent phenotypes.

Indexed as

TranscriptomeVascular StiffnessAortaCell MovementCell ProliferationCells, CulturedCluster AnalysisComputational BiologyCoronary VesselsData MiningExtracellular MatrixGene Expression ProfilingGene Expression RegulationHumansHydrogelsMechanotransduction, CellularHydrogelsMALAT1 long non-coding RNA, humanRNA, Long Noncodingaortacoronary artery diseaseextracellular matrixlncRNAtranscriptomevascular smooth musclevascular stiffness

Identifiers

PMID29051139
PMCPMC5881588

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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.