Evidence map›Paper›PMID 37589136›Full record

ArticleArteriosclerosis, thrombosis, and vascular biology2023

Female Gene Networks Are Expressed in Myofibroblast-Like Smooth Muscle Cells in Vulnerable Atherosclerotic Plaques.

Ernest Diez Benavente, Santosh Karnewar, Michele Buono, Eloi Mili, Robin J G Hartman, Daniek Kapteijn, Lotte Slenders, Mark Daniels, Redouane Aherrahrou, Tobias Reinberger and 14 more

Open access · hybridAbstract read
In one paragraph

Article in Arteriosclerosis, thrombosis, and vascular biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
4.2field-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

14 citing papers in PubMed, 27 citations in OpenAlex.

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  7. Women's heart disease research in the netherlands: angina with non-obstructive coronary artery disease and beyond.Netherlands heart journal : monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation · 2025
    Review
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  14. Phenotypic Switching of Vascular Smooth Muscle Cells in Atherosclerosis.Journal of the American Heart Association · 2023
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

24 authors at 8 institutions in 5 countries.

Ernest Diez BenaventeLaboratory of Experimental Cardiology (E.D.B., M.B., E.M., R.J.G.H., D.K., M.D., H.M.d.R.), University Medical Centre Utrecht, Utrecht University, the Netherlands.ORCID 0000-0002-4313-4290
Santosh KarnewarRobert M. Berne Cardiovascular Research Center (S.K., G.K.O.), University of Virginia, Charlottesville.
Michele BuonoLaboratory of Experimental Cardiology (E.D.B., M.B., E.M., R.J.G.H., D.K., M.D., H.M.d.R.), University Medical Centre Utrecht, Utrecht University, the Netherlands.
Eloi MiliLaboratory of Experimental Cardiology (E.D.B., M.B., E.M., R.J.G.H., D.K., M.D., H.M.d.R.), University Medical Centre Utrecht, Utrecht University, the Netherlands.ORCID 0000-0002-9070-9851
Robin J G HartmanLaboratory of Experimental Cardiology (E.D.B., M.B., E.M., R.J.G.H., D.K., M.D., H.M.d.R.), University Medical Centre Utrecht, Utrecht University, the Netherlands.
Daniek KapteijnLaboratory of Experimental Cardiology (E.D.B., M.B., E.M., R.J.G.H., D.K., M.D., H.M.d.R.), University Medical Centre Utrecht, Utrecht University, the Netherlands.
Lotte SlendersCentral Diagnostic Laboratory (L.S., M.M., G.P.), University Medical Centre Utrecht, Utrecht University, the Netherlands.ORCID 0000-0003-3794-7604
Mark DanielsLaboratory of Experimental Cardiology (E.D.B., M.B., E.M., R.J.G.H., D.K., M.D., H.M.d.R.), University Medical Centre Utrecht, Utrecht University, the Netherlands.
Redouane AherrahrouCenter for Public Health Genomics (R.A., M.C.), University of Virginia, Charlottesville.
Tobias ReinbergerInstitute for Cardiogenetics, University of Lübeck, Germany (R.A., T.R., J.E.).ORCID 0000-0002-6237-0803
Barend M MolDepartment of Vascular Surgery (B.M.M., G.J.d.B., D.P.V.d.K.), University Medical Centre Utrecht, Utrecht University, the Netherlands.
Gert J de BorstDepartment of Vascular Surgery (B.M.M., G.J.d.B., D.P.V.d.K.), University Medical Centre Utrecht, Utrecht University, the Netherlands.ORCID 0000-0002-1389-4141
Dominique P V de KleijnDepartment of Vascular Surgery (B.M.M., G.J.d.B., D.P.V.d.K.), University Medical Centre Utrecht, Utrecht University, the Netherlands.
Koen H M PrangeExperimental Vascular Biology, Department of Medical Biochemistry, Amsterdam University Medical Centers - location AMC, University of Amsterdam, Netherlands (K.H.M.P., M.P.J.d.W.).
Marie A C DepuydtDivision of BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, the Netherlands (M.A.C.D., J.K.).
Menno P J de WintherExperimental Vascular Biology, Department of Medical Biochemistry, Amsterdam University Medical Centers - location AMC, University of Amsterdam, Netherlands (K.H.M.P., M.P.J.d.W.).
Johan KuiperDivision of BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, the Netherlands (M.A.C.D., J.K.).ORCID 0000-0001-5834-690X
Johan L M BjörkegrenDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York (J.L.M.B.).
Jeanette ErdmannInstitute for Cardiogenetics, University of Lübeck, Germany (R.A., T.R., J.E.).ORCID 0000-0002-4486-6231
Mete CivelekCenter for Public Health Genomics (R.A., M.C.), University of Virginia, Charlottesville.ORCID 0000-0002-8141-0284
Michal MokryCentral Diagnostic Laboratory (L.S., M.M., G.P.), University Medical Centre Utrecht, Utrecht University, the Netherlands.ORCID 0000-0002-5298-4852
Gary K OwensRobert M. Berne Cardiovascular Research Center (S.K., G.K.O.), University of Virginia, Charlottesville.ORCID 0000-0002-7119-9657
Gerard PasterkampCentral Diagnostic Laboratory (L.S., M.M., G.P.), University Medical Centre Utrecht, Utrecht University, the Netherlands.ORCID 0000-0001-5345-1022
Hester M den RuijterLaboratory of Experimental Cardiology (E.D.B., M.B., E.M., R.J.G.H., D.K., M.D., H.M.d.R.), University Medical Centre Utrecht, Utrecht University, the Netherlands.ORCID 0000-0001-9762-014X
University Medical Center Utrecht · NLUtrecht University · NLUniversity of Virginia · USAmsterdam University Medical Centers · NLCentre for Human Drug Research · NLUniversity of Lübeck · DEKarolinska University Hospital · SEUniversity of Eastern Finland · FI

Funding

BASIC CARDIOVASCULAR RESEARCH TRAINING GRANTT32HL007284 · NHLBI · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI Brant E Isakson, Gary K Owens · 1985 to 2026
$19.6M
Role of Smooth Muscle Cell Insulin Resistance and Systemic Metabolic Dysfunction in Atherosclerosis Development and Late Stage Lesion PathogenesisR01HL166161 · NHLBI · UNIVERSITY OF VIRGINIA · PI Gary K Owens · 2023 to 2026
$3.2M
Endothelial Cell to Mesenchymal Cell Transitions Play a Critical Biological Sex- and Aging-Dependent Role in Formation and Maintenance of the Acta2+ Atherosclerotic Lesion Protective Fibrous CapR01HL156849 · NHLBI · UNIVERSITY OF VIRGINIA · PI OWENS, GARY K · 2022 to 2025
$3.2M
IL1beta signaling in SMCpromotes beneficial changes in late stage atherosclerotic lesion pathogenesisR01HL141425 · NHLBI · UNIVERSITY OF VIRGINIA · PI OWENS, GARY K · 2019 to 2022
$3.1M
Defining SMC phenotypes critical in late stage atherosclerosis pathogenesisR01HL136314 · NHLBI · UNIVERSITY OF VIRGINIA · PI OWENS, GARY K · 2018 to 2021
$3.0M
NHLBI NIH HHS R01 HL136314NHLBI NIH HHS R01 HL141425NHLBI NIH HHS R01 HL156849NHLBI NIH HHS R01 HL166161NHLBI NIH HHS T32 HL007284
6 · The paper itself

Abstract

backgroundWomen presenting with coronary artery disease more often present with fibrous atherosclerotic plaques, which are currently understudied. Phenotypically modulated smooth muscle cells (SMCs) contribute to atherosclerosis in women. How these phenotypically modulated SMCs shape female versus male plaques is unknown.

methodsGene regulatory networks were created using RNAseq gene expression data from human carotid atherosclerotic plaques. The networks were prioritized based on sex bias, relevance for smooth muscle biology, and coronary artery disease genetic enrichment. Network expression was linked to histologically determined plaque phenotypes. In addition, their expression in plaque cell types was studied at single-cell resolution using single-cell RNAseq. Finally, their relevance for disease progression was studied in female and male

resultsHere, we identify multiple sex-stratified gene regulatory networks from human carotid atherosclerotic plaques. Prioritization of the female networks identified 2 main SMC gene regulatory networks in late-stage atherosclerosis. Single-cell RNA sequencing mapped these female networks to 2 SMC phenotypes: a phenotypically modulated myofibroblast-like SMC network and a contractile SMC network. The myofibroblast-like network was mostly expressed in plaques that were vulnerable in women. Finally, the mice ortholog of key driver gene

conclusionsFemale atherosclerosis is characterized by gene regulatory networks that are active in fibrous vulnerable plaques rich in myofibroblast-like SMCs.

Indexed as

AtherosclerosisCoronary Artery DiseasePlaque, AtheroscleroticAnimalsFemaleGene Regulatory NetworksHumansMaleMiceMyocytes, Smooth MuscleMyofibroblastscoronary artery diseasegene expressionlipidsplaquewomen's health

Identifiers

PMID37589136
PMCPMC10521798
OpenAlexW4385897580

What Socratic holds

Textmetadata
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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 Socratic graph.