Evidence map›Paper›PMID 28973892›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2017

Systems biology analysis of longitudinal functional response of endothelial cells to shear stress.

Nassim E Ajami, Shakti Gupta, Mano R Maurya, Phu Nguyen, Julie Yi-Shuan Li, John Y-J Shyy, Zhen Chen, Shu Chien, Shankar Subramaniam

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.

0numbers the graph read from it
0cells of the map it votes in
87citing 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

87 citing papers in PubMed.

  1. Article
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  8. A comprehensive review of m6 A methylation in coronary heart disease.Journal of molecular medicine (Berlin, Germany) · 2025
    Review
  9. METTL3 mediates atheroprone flow-induced glycolysis in endothelial cells.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  10. Article
  11. Pulsatile flow induces chromatin interaction with lamin-associated proteins to enrich H3K9 methylation in endothelial cells.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  12. Article
  13. Article
  14. Review
  15. Review
  16. Article
  17. Article
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  20. Article

27 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

9 authors.

Nassim E AjamiBioinformatics and Systems Biology Graduate Program, University of California at San Diego, La Jolla, CA 92023.
Shakti GuptaDepartment of Bioengineering, University of California at San Diego, La Jolla, CA 92093.
Mano R MauryaDepartment of Bioengineering, University of California at San Diego, La Jolla, CA 92093.
Phu NguyenDepartment of Bioengineering, University of California at San Diego, La Jolla, CA 92093.
Julie Yi-Shuan LiDepartment of Bioengineering, University of California at San Diego, La Jolla, CA 92093.
John Y-J ShyyDepartment of Medicine, University of California at San Diego, La Jolla, CA 92093; jshyy@ucsd.edu zhenchen@coh.org shuchien@ucsd.edu shankar@ucsd.edu.
Zhen ChenDepartment of Medicine, University of California at San Diego, La Jolla, CA 92093; jshyy@ucsd.edu zhenchen@coh.org shuchien@ucsd.edu shankar@ucsd.edu.
Shu ChienDepartment of Bioengineering, University of California at San Diego, La Jolla, CA 92093; jshyy@ucsd.edu zhenchen@coh.org shuchien@ucsd.edu shankar@ucsd.edu.
Shankar SubramaniamBioinformatics and Systems Biology Graduate Program, University of California at San Diego, La Jolla, CA 92023; jshyy@ucsd.edu zhenchen@coh.org shuchien@ucsd.edu shankar@ucsd.edu.

Funding

Systems Biological Analysis of Innate and Adaptive Responses to VaccinationU19AI090023 · NIAID · EMORY UNIVERSITY · PI AHMED, RAFI, LI, SHUZHAO · 2010 to 2021
$45.0M
Systems Biology Analyses for Hemodynamic Regulation of Vascular HomeostasisR01HL108735 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHIEN, SHU, SHYY, JOHN YJ · 2012 to 2024
$13.4M
Shear Regulation of MicroRNA Transportomes and Targetomes in Vascular HomeostasisR01HL106579 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHIEN, SHU, SHYY, JOHN YJ · 2011 to 2022
$8.3M
GRADUATE TRAINING PROGRAM IN BIONFORMATICST32GM008806 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BAFNA, VINEET, REN, BING · 2001 to 2020
$6.2M
Theoretical Foundations and Software Infrastructure for Biological Network DatabasesU01CA198941 · NCI · CASE WESTERN RESERVE UNIVERSITY · PI KOYUTURK, MEHMET · 2015 to 2017
$1.4M
Hypoxia-Suppressed Dicer and AGO1 Promote AngiogenesisR00HL122368 · NHLBI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI CHEN, ZHEN BOUMAN · 2017 to 2019
$747k
Hypoxia-Suppressed Dicer and AGO1 Promote AngiogenesisK99HL122368 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHEN, ZHEN BOUMAN · 2014 to 2015
$268k
NCI NIH HHS U01 CA198941NHLBI NIH HHS K99 HL122368NHLBI NIH HHS R00 HL122368NHLBI NIH HHS R01 HL106579NHLBI NIH HHS R01 HL108735NIAID NIH HHS U19 AI090023NIGMS NIH HHS T32 GM008806
6 · The paper itself

Abstract

Blood flow and vascular shear stress patterns play a significant role in inducing and modulating physiological responses of endothelial cells (ECs). Pulsatile shear (PS) is associated with an atheroprotective endothelial phenotype, while oscillatory shear (OS) is associated with an atheroprone endothelial phenotype. Although mechanisms of endothelial shear response have been extensively studied, most studies focus on characterization of single molecular pathways, mainly at fixed time points after stress application. Here, we carried out a longitudinal time-series study to measure the transcriptome after the application of PS and OS. We performed systems analyses of transcriptional data of cultured human vascular ECs to elucidate the dynamics of endothelial responses in several functional pathways such as cell cycle, oxidative stress, and inflammation. By combining the temporal data on differentially expressed transcription factors and their targets with existing knowledge on relevant functional pathways, we infer the causal relationships between disparate endothelial functions through common transcriptional regulation mechanisms. Our study presents a comprehensive temporally longitudinal experimental study and mechanistic model of shear stress response. By comparing the relative endothelial expressions of genes between OS and PS, we provide insights and an integrated perspective into EC function in response to differential shear. This study has significant implications for the pathogenesis of vascular diseases.

Indexed as

Gene Expression RegulationPulsatile FlowStress, MechanicalTranscriptomeCell CycleCells, CulturedEndothelium, VascularEpithelial-Mesenchymal TransitionHumansHuman Umbilical Vein Endothelial CellsInflammationOxidative StressSystems BiologyTranscription FactorsTranscription Factorsendothelial cellsRNA-seqshear stresssystems biologytime-series analysis

Identifiers

PMID28973892
PMCPMC5642700

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.