Evidence map›Paper›PMID 34178388›Full record

ArticleImmunometabolism2021

Meta-Analysis of Smooth Muscle Lineage Transcriptomes in Atherosclerosis and Their Relationships to In Vitro Models.

Austin C Conklin, Hitoo Nishi, Florencia Schlamp, Tiit Örd, Kadri Õunap, Minna U Kaikkonen, Edward A Fisher, Casey E Romanoski

Open access · diamondAbstract read
In one paragraph

Article in Immunometabolism, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed, 2 pooled it
3.2field-weighted citation impact, top 7% 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

36 citing papers in PubMed, 2 syntheses or guidelines pooled it, 62 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Review
  4. Article
  5. Article
  6. PERK Is Dispensable for Smooth Muscle Cell Phenotype Switching in Atherosclerosis.Arteriosclerosis, thrombosis, and vascular biology · 2026
    Article
  7. Article
  8. Article
  9. Review
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  11. Article
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  14. Article
  15. Single-Cell Multimodal Profiling Reveals a Novel CD26Arteriosclerosis, thrombosis, and vascular biology · 2025
    Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. High-Dimensional Single-Cell Multimodal Landscape of Human Carotid Atherosclerosis.Arteriosclerosis, thrombosis, and vascular biology · 2024
    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

8 authors at 3 institutions in 2 countries.

Austin C ConklinThe Department of Cellular and Molecular Medicine, The University of Arizona, Tucson, AZ 85721, USA.
Hitoo NishiThe Cardiovascular Research Center, Division of Cardiology, Department of Medicine, NYU Grossman School of Medicine, New York, NY 10016, USA.
Florencia SchlampThe Cardiovascular Research Center, Division of Cardiology, Department of Medicine, NYU Grossman School of Medicine, New York, NY 10016, USA.
Tiit ÖrdA. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio 70211, Finland.
Kadri ÕunapA. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio 70211, Finland.
Minna U KaikkonenA. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio 70211, Finland.
Edward A FisherThe Cardiovascular Research Center, Division of Cardiology, Department of Medicine, NYU Grossman School of Medicine, New York, NY 10016, USA.
Casey E RomanoskiThe Department of Cellular and Molecular Medicine, The University of Arizona, Tucson, AZ 85721, USA.
New York University · USUniversity of Eastern Finland · FIUniversity of Arizona · US

Funding

SOUTHWEST ENVIRONMENTAL HEALTH SCIENCES CENTERP30ES006694 · NIEHS · UNIVERSITY OF ARIZONA · PI DEAN BILLHEIMER · 1994 to 2026
$36.7M
PHYSIOLOGYT32HL007249 · NHLBI · UNIVERSITY OF ARIZONA · PI Brett A Colson, JOHN P KONHILAS · 1985 to 2026
$12.5M
Molecular Regulation of Atherosclerosis Regression - RenewalR01HL084312 · NHLBI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI FISHER, EDWARD A · 2006 to 2024
$11.4M
HDL and atherosclerosis regressionR01HL129433 · NHLBI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI FISHER, EDWARD A, MOORE, KATHRYN J · 2016 to 2019
$2.4M
Mechanisms of ERG in Endothelial ActivationR01HL147187 · NHLBI · UNIVERSITY OF ARIZONA · PI ROMANOSKI, CASEY E · 2019 to 2023
$1.9M
NHLBI NIH HHS R01 HL084312NHLBI NIH HHS R01 HL129433NHLBI NIH HHS R01 HL147187NHLBI NIH HHS T32 HL007249NIEHS NIH HHS P30 ES006694
6 · The paper itself

Abstract

backgroundVascular smooth muscle cells (VSMC) exhibit phenotypic plasticity in atherosclerotic plaques, and among other approaches, has been modeled in vitro by cholesterol loading.

methodsMeta-analysis of scRNA-seq data from VSMC lineage traced cells across five experiments of murine atherosclerosis was performed. In vivo expression profiles were compared to three in vitro datasets of VSMCs loaded with cholesterol and three datasets of polarized macrophages.

resultsWe identified 24 cell clusters in the meta-analysis of single cells from mouse atherosclerotic lesions with notable heterogeneity across studies, especially for macrophage populations. Trajectory analysis of VSMC lineage positive cells revealed several possible paths of state transitions with one traversing from contractile VSMC to macrophages by way of a proliferative cell cluster. Transcriptome comparisons between in vivo and in vitro states underscored that data from three in vitro cholesterol-treated VSMC experiments did not mirror cell state transitions observed in vivo. However, all in vitro macrophage profiles analyzed (M1, M2, and oxLDL) were more similar to in vivo profiles of macrophages than in vitro VSMCs were to in vivo profiles of VSMCs. oxLDL loaded macrophages showed the most similarity to in vivo states. In contrast to the in vitro data, comparison between mouse and human in vivo data showed many similarities.

conclusionsIdentification of the sources of variation across single cell datasets in atherosclerosis will be an important step towards understanding VSMC fate transitions in vivo. Also, we conclude that cholesterol-loading in vitro is insufficient to model the VSMC cell state transitions observed in vivo, which underscores the need to develop better cell models. Mouse models, however, appear to reproduce a number of the features of VSMCs in human plaques.

Indexed as

atherosclerosischolesterollineage tracingmacrophagessingle cell RNA-seqsmooth muscle cells

Identifiers

PMID34178388
PMCPMC8232871
OpenAlexW3163980044

What OpenQuestion holds

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LicenceCC BY
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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.