Evidence map›Paper›PMID 38385291›Full record

ArticleArteriosclerosis, thrombosis, and vascular biology2024

High-Dimensional Single-Cell Multimodal Landscape of Human Carotid Atherosclerosis.

Alexander C Bashore, Hanying Yan, Chenyi Xue, Lucie Y Zhu, Eunyoung Kim, Thomas Mawson, Johana Coronel, Allen Chung, Nadja Sachs, Sebastian Ho and 7 more

Open access · greenAbstract read
In one paragraph

Article in Arteriosclerosis, thrombosis, and vascular biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.

0numbers the graph read from it
0cells of the map it votes in
83citing papers in PubMed
18.3field-weighted citation impact, top 1% 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

83 citing papers in PubMed, 76 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Atherosclerotic Cell Fates: A Single-Cell View of ER Stress.Journal of cardiovascular development and disease · 2026
    Review
  5. Review
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. PERK Is Dispensable for Smooth Muscle Cell Phenotype Switching in Atherosclerosis.Arteriosclerosis, thrombosis, and vascular biology · 2026
    Article
  13. Article
  14. Article
  15. Review
  16. Review
  17. Article
  18. [Dual role and therapeutic potential of TREM2 in atherosclerosis].Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2026
    Review
  19. Review
  20. CD8Nature reviews. Cardiology · 2026
    Review

23 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors at 6 institutions in 4 countries.

Alexander C Bashore *Division of Cardiology, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY (A.C.B., C.X., L.Y.Z., E.K., T.M., J.C., A.C., S.H., L.S.R., R.C.B., M.P.R.).ORCID 0000-0002-1380-9242
Hanying Yan *Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia (H.Y., M.L.).ORCID 0000-0002-9227-1742
Chenyi XueDivision of Cardiology, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY (A.C.B., C.X., L.Y.Z., E.K., T.M., J.C., A.C., S.H., L.S.R., R.C.B., M.P.R.).
Lucie Y ZhuDivision of Cardiology, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY (A.C.B., C.X., L.Y.Z., E.K., T.M., J.C., A.C., S.H., L.S.R., R.C.B., M.P.R.).ORCID 0000-0002-1048-5377
Eunyoung KimDivision of Cardiology, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY (A.C.B., C.X., L.Y.Z., E.K., T.M., J.C., A.C., S.H., L.S.R., R.C.B., M.P.R.).ORCID 0000-0002-9749-9930
Thomas MawsonDivision of Cardiology, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY (A.C.B., C.X., L.Y.Z., E.K., T.M., J.C., A.C., S.H., L.S.R., R.C.B., M.P.R.).
Johana CoronelDivision of Cardiology, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY (A.C.B., C.X., L.Y.Z., E.K., T.M., J.C., A.C., S.H., L.S.R., R.C.B., M.P.R.).ORCID 0000-0002-9257-0849
Allen ChungDivision of Cardiology, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY (A.C.B., C.X., L.Y.Z., E.K., T.M., J.C., A.C., S.H., L.S.R., R.C.B., M.P.R.).ORCID 0000-0002-2494-9179
Nadja SachsDepartment of Vascular and Endovascular Surgery, Technical University Munich, Germany (N.S., L.M.).ORCID 0000-0001-8031-017X
Sebastian HoDivision of Cardiology, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY (A.C.B., C.X., L.Y.Z., E.K., T.M., J.C., A.C., S.H., L.S.R., R.C.B., M.P.R.).
Leila S RossDivision of Cardiology, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY (A.C.B., C.X., L.Y.Z., E.K., T.M., J.C., A.C., S.H., L.S.R., R.C.B., M.P.R.).ORCID 0000-0003-4360-5213
Michael KissnerColumbia Stem Cell Initiative, Department of Genetics and Development (M.K., E.P.), Columbia University Irving Medical Center, New York, NY.
Emmanuelle PasseguéColumbia Stem Cell Initiative, Department of Genetics and Development (M.K., E.P.), Columbia University Irving Medical Center, New York, NY.ORCID 0000-0002-3516-297X
Robert C BauerDivision of Cardiology, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY (A.C.B., C.X., L.Y.Z., E.K., T.M., J.C., A.C., S.H., L.S.R., R.C.B., M.P.R.).
Lars MaegdefesselDepartment of Vascular and Endovascular Surgery, Technical University Munich, Germany (N.S., L.M.).ORCID 0000-0001-5228-2634
Mingyao Li *Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia (H.Y., M.L.).ORCID 0000-0003-2422-9494
Muredach P Reilly *Division of Cardiology, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY (A.C.B., C.X., L.Y.Z., E.K., T.M., J.C., A.C., S.H., L.S.R., R.C.B., M.P.R.).
Columbia University · USColumbia University Irving Medical Center · USUniversity of Pennsylvania · USI.R.C.C.S. Oasi Maria SS · ITKarolinska Institutet · SETechnical University of Munich · DE

Funding

Tumor Biology and Microenvironment ProgramP30CA013696 · NCI · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI Anil K Rustgi · 1985 to 2026
$115.3M
Clinical and Translational Science AwardUL1TR001873 · NCATS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI REILLY, MUREDACH P · 2016 to 2025
$99.0M
POSTDOCTORAL TRAINING IN ARTERIOSCLEROSIS RESEARCHT32HL007343 · NHLBI · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI HENRY N GINSBERG, Muredach P Reilly · 1985 to 2026
$12.7M
Elucidation of Tissue-Specific Transcriptomic Profiles in Cardiometabolic DiseaseR01HL113147 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI LI, MINGYAO, REILLY, MUREDACH P · 2012 to 2022
$6.8M
Smooth muscle cell-derived cell fates and cellular interactions in atherosclerotic plaque stability in disease progression and regression.R01HL166916 · NHLBI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Muredach P Reilly · 2023 to 2026
$2.8M
Computational and functional strategies to decipher lncRNAs in human atherosclerosisR01HL150359 · NHLBI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI LI, MINGYAO, REILLY, MUREDACH P · 2020 to 2023
$2.7M
Identification of smooth muscle cell genes causal in atherosclerotic plaque stability and cardiovascular disease riskR01HL169766 · NHLBI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Muredach P Reilly, Danish Saleheen · 2023 to 2026
$2.6M
Molecular Mechanisms of TRIB1 Regulation of Hepatic MetabolismR01DK134026 · NIDDK · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Robert Clayton Bauer · 2023 to 2026
$2.5M
Regulation of lipoprotein metabolism by adipose-specific Tribbles-1R01HL141745 · NHLBI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI BAUER, ROBERT CLAYTON · 2018 to 2022
$2.0M
Statistical Methods for Single-Cell TranscriptomicsR01GM125301 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI LI, MINGYAO, ZHANG, NANCY R · 2017 to 2020
$1.5M
Integrative analysis of bulk and single-cell RNA-seq data for cardiometabolic diseaseR21HL156234 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI LI, MINGYAO · 2021 to 2022
$244k
NCATS NIH HHS UL1 TR001873NCI NIH HHS P30 CA013696NHLBI NIH HHS R01 HL113147NHLBI NIH HHS R01 HL141745NHLBI NIH HHS R01 HL150359NHLBI NIH HHS R01 HL166916NHLBI NIH HHS R01 HL169766NHLBI NIH HHS R21 HL156234NHLBI NIH HHS T32 HL007343NIDDK NIH HHS R01 DK134026NIGMS NIH HHS R01 GM125301
6 · The paper itself

Abstract

backgroundAtherosclerotic plaques are complex tissues composed of a heterogeneous mixture of cells. However, our understanding of the comprehensive transcriptional and phenotypic landscape of the cells within these lesions is limited.

methodsTo characterize the landscape of human carotid atherosclerosis in greater detail, we combined cellular indexing of transcriptomes and epitopes by sequencing and single-cell RNA sequencing to classify all cell types within lesions (n=21; 13 symptomatic) to achieve a comprehensive multimodal understanding of the cellular identities of atherosclerosis and their association with clinical pathophysiology.

resultsWe identified 25 cell populations, each with a unique multiomic signature, including macrophages, T cells, NK (natural killer) cells, mast cells, B cells, plasma cells, neutrophils, dendritic cells, endothelial cells, fibroblasts, and smooth muscle cells (SMCs). Among the macrophages, we identified 2 proinflammatory subsets enriched in IL-1B (interleukin-1B) or C1Q expression, 2 TREM2-positive foam cells (1 expressing inflammatory genes), and subpopulations with a proliferative gene signature and SMC-specific gene signature with fibrotic pathways upregulated. Further characterization revealed various subsets of SMCs and fibroblasts, including SMC-derived foam cells. These foamy SMCs were localized in the deep intima of coronary atherosclerotic lesions. Utilizing cellular indexing of transcriptomes and epitopes by sequencing data, we developed a flow cytometry panel, using cell surface proteins CD29, CD142, and CD90, to isolate SMC-derived cells from lesions. Lastly, we observed reduced proportions of efferocytotic macrophages, classically activated endothelial cells, and contractile and modulated SMC-derived cells, while inflammatory SMCs were enriched in plaques of clinically symptomatic versus asymptomatic patients.

conclusionsOur multimodal atlas of cell populations within atherosclerosis provides novel insights into the diversity, phenotype, location, isolation, and clinical relevance of the unique cellular composition of human carotid atherosclerosis. These findings facilitate both the mapping of cardiovascular disease susceptibility loci to specific cell types and the identification of novel molecular and cellular therapeutic targets for the treatment of the disease.

Indexed as

AtherosclerosisCarotid Artery DiseasesPlaque, AtheroscleroticEndothelial CellsEpitopesHumansMyocytes, Smooth MuscleEpitopesatherosclerosisfibroblastsmacrophagesingle-cell analysissmooth muscle cell

Identifiers

PMID38385291
PMCPMC10978277
OpenAlexW4392080105

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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.