Evidence map›Paper›PMID 36662769›Full record

ArticlePloS one2023

Co-culture models of endothelial cells, macrophages, and vascular smooth muscle cells for the study of the natural history of atherosclerosis.

Martin Liu, Saurabhi Samant, Charu Hasini Vasa, Ryan M Pedrigi, Usama M Oguz, Sangjin Ryu, Timothy Wei, Daniel R Anderson, Devendra K Agrawal, Yiannis S Chatzizisis

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 1 pooled it
4.4field-weighted citation impact, top 5% 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

19 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. CD8Nature reviews. Cardiology · 2026
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  6. Key parameters for designing robust 2D and 3D spheroid models forBioengineering & translational medicine · 2025
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  8. Review
  9. Review
  10. IntermedinJournal of inflammation research · 2025
    Article
  11. Review
  12. Review
  13. Article
  14. Review
  15. Review
  16. Effects of Mechanical Stress on Endothelial Cells In Situ and In Vitro.International journal of molecular sciences · 2023
    Review
  17. Article
  18. Article
  19. Article
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 4 institutions in 1 country.

Martin LiuDivision of Cardiovascular Medicine, Miller School of Medicine, University of Miami, Miami, Florida, United States of America.
Saurabhi SamantCardiovascular Division, University of Nebraska Medical Center, Omaha, Nebraska, United States of America.
Charu Hasini VasaDivision of Cardiovascular Medicine, Miller School of Medicine, University of Miami, Miami, Florida, United States of America.
Ryan M PedrigiDepartment of Biological System Engineering, University of Nebraska-Lincoln, Lincoln, Nebraska, United States of America.
Usama M OguzDivision of Cardiovascular Medicine, Miller School of Medicine, University of Miami, Miami, Florida, United States of America.
Sangjin RyuDepartment of Mechanical and Materials Engineering, College of Engineering, University of Nebraska-Lincoln, Lincoln, Nebraska, United States of America.
Timothy WeiDepartment of Mechanical and Materials Engineering, College of Engineering, University of Nebraska-Lincoln, Lincoln, Nebraska, United States of America.
Daniel R AndersonCardiovascular Division, University of Nebraska Medical Center, Omaha, Nebraska, United States of America.
Devendra K AgrawalDepartment of Translational Research, Western University of Health Science, Pomona, California, United States of America.
Yiannis S ChatzizisisDivision of Cardiovascular Medicine, Miller School of Medicine, University of Miami, Miami, Florida, United States of America.ORCID 0000-0001-8955-0081
University of Miami · USUniversity of Nebraska–Lincoln · USUniversity of Nebraska Medical Center · USWestern University of Health Sciences · US

Funding

Patient-Specific Simulations to Guide Coronary Bifurcation StentingR01HL144690 · NHLBI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI CHATZIZISIS, IOANNIS S · 2019 to 2023
$3.9M
NHLBI NIH HHS R01 HL144690
6 · The paper itself

Abstract

backgroundThis work aims to present a fast, affordable, and reproducible three-cell co-culture system that could represent the different cellular mechanisms of atherosclerosis, extending from atherogenesis to pathological intimal thickening. METHODS AND

resultsWe built four culture models: (i) Culture model #1 (representing normal arterial intima), where human coronary artery endothelial cells were added on top of Matrigel-coated collagen type I matrix, (ii) Culture model #2 (representing atherogenesis), which demonstrated the subendothelial accumulation and oxidative modification of low-density lipoproteins (LDL), (iii) Culture model #3 (representing intimal xanthomas), which demonstrated the monocyte adhesion to the endothelial cell monolayer, transmigration into the subendothelial space, and transformation to lipid-laden macrophages, (iv) Culture model #4 (representing pathological intimal thickening), which incorporated multiple layers of human coronary artery smooth muscle cells within the matrix. Coupling this model with different shear stress conditions revealed the effect of low shear stress on the oxidative modification of LDL and the upregulation of pro-inflammatory molecules and matrix-degrading enzymes. Using electron microscopy, immunofluorescence confocal microscopy, protein and mRNA quantification assays, we showed that the behaviors exhibited by the endothelial cells, macrophages and vascular smooth muscle cells in these models were very similar to those exhibited by these cell types in nascent and intermediate atherosclerotic plaques in humans. The preparation time of the cultures was 24 hours.

conclusionWe present three-cell co-culture models of human atherosclerosis. These models have the potential to allow cost- and time-effective investigations of the mechanobiology of atherosclerosis and new anti-atherosclerotic drug therapies.

Indexed as

AtherosclerosisEndothelial CellsCoculture TechniquesHumansMacrophagesMuscle, Smooth, VascularMyocytes, Smooth Muscle

Identifiers

PMID36662769
PMCPMC9858056
OpenAlexW4317567273

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.