Evidence map›Paper›PMID 34417174›Full record

ArticleScience advances2021

Single-cell RNA-seq reveals a critical role of novel pro-inflammatory EndMT in mediating adverse remodeling in coronary artery-on-a-chip.

Peng Zhao, Qingzhou Yao, Pei-Jian Zhang, Erlinda The, Yufeng Zhai, Lihua Ao, Michael J Jarrett, Charles A Dinarello, David A Fullerton, Xianzhong Meng

Open access · goldAbstract read
In one paragraph

Article in Science advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed, 1 pooled it
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

26 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Article
  5. Review
  6. Review
  7. Engineering in vitro vascular microsystems.Microsystems & nanoengineering · 2025
    Review
  8. Review
  9. Review
  10. 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
  11. Review
  12. Whys and Wherefores of Coronary Arterial Positive Remodeling.Arteriosclerosis, thrombosis, and vascular biology · 2024
    Review
  13. Article
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  15. Review
  16. 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

10 authors at 1 institution in 1 country.

Peng ZhaoDepartment of Surgery, University of Colorado Denver, Aurora, CO, USA.ORCID 0000-0003-3499-1415
Qingzhou YaoDepartment of Surgery, University of Colorado Denver, Aurora, CO, USA.
Pei-Jian ZhangDepartment of Surgery, University of Colorado Denver, Aurora, CO, USA.
Erlinda TheDepartment of Surgery, University of Colorado Denver, Aurora, CO, USA.
Yufeng ZhaiDepartment of Surgery, University of Colorado Denver, Aurora, CO, USA.
Lihua AoDepartment of Surgery, University of Colorado Denver, Aurora, CO, USA.
Michael J JarrettDepartment of Surgery, University of Colorado Denver, Aurora, CO, USA.ORCID 0000-0003-2959-8555
Charles A DinarelloDepartment of Medicine, University of Colorado Denver, Aurora, CO, USA.
David A FullertonDepartment of Surgery, University of Colorado Denver, Aurora, CO, USA.ORCID 0000-0002-6895-6354
Xianzhong MengDepartment of Surgery, University of Colorado Denver, Aurora, CO, USA. x.meng@cuanschutz.edu.ORCID 0000-0002-0201-1008
University of Colorado Denver · US

Funding

University of Colorado Anschutz Medical Campus DRCP30DK116073 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI LORI SUSSEL · 2020 to 2026
$10.8M
ZEBRAFISH TRANSGENIC CORE - ROCKY MOUNTAIN NEUROLOGICAL DISORDERS CORE CENTERP30NS048154 · NINDS · UNIVERSITY OF COLORADO DENVER · PI RIBERA, ANGELES BADELL · 2004 to 2020
$10.1M
Role of inflammatory response in aortic valve lesionsR01HL106582 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI MENG, XIANZHONG · 2011 to 2020
$3.8M
Suppression of AVIC inflammosteogenesis for prevention of CAVD progressionR01HL121776 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI MENG, XIANZHONG · 2015 to 2023
$3.6M
NHLBI NIH HHS R01 HL106582NHLBI NIH HHS R01 HL121776NIDDK NIH HHS P30 DK116073NINDS NIH HHS P30 NS048154
6 · The paper itself

Abstract

A three-dimensional microengineered human coronary artery-on-a-chip was developed for investigation of the mechanism by which low and oscillatory shear stress (OSS) induces pro-atherogenic changes. Single-cell RNA sequencing revealed that OSS induced distinct changes in endothelial cells (ECs) including pro-inflammatory endothelial-to-mesenchymal transition (EndMT). OSS promoted pro-inflammatory EndMT through the Notch1/p38 MAPK-NF-κB signaling axis. Moreover, OSS-induced EC phenotypic changes resulted in proliferation and extracellular matrix (ECM) protein up-regulation in smooth muscle cells (SMCs) through the RANTES-mediated paracrine mechanism. IL-37 suppressed OSS-induced pro-inflammatory EndMT and thereby abrogated SMC proliferation and ECM protein remodeling. Overall, this study provides insights into endothelial heterogeneity under atheroprone shear stress and identifies the mechanistic role of a novel EC subtype in promoting adverse vascular remodeling. Further, this study demonstrates that anti-inflammatory approach is capable of mitigating vascular pathobiology evoked by atheroprone shear stress.

Indexed as

Coronary VesselsEndothelial CellsCells, CulturedExtracellular Matrix ProteinsHumansLab-On-A-Chip DevicesRNA-SeqExtracellular Matrix Proteins

Identifiers

PMID34417174
PMCPMC8378826
OpenAlexW3195302873

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

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.