ArticleNature cardiovascular research2025
Single-cell RNA sequencing reveals sex differences in the subcellular composition and associated gene-regulatory network activity of human carotid plaques.
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Article in Nature cardiovascular research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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18citing papers in PubMed, 1 pooled it
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Candidate Biomarkers Linking Periodontitis with Atherosclerotic and Related Cardiovascular Phenotypes: A Systematic Review Focused on Sex-Specific Evidence.International journal of molecular sciences · 2026Pooled it
- Cell-Surface Signatures and Targets of Modulated Vascular Smooth Muscle Cells in Atherosclerosis: From State Identification to Precision Intervention.Journal of cardiovascular development and disease · 2026Review
- Metabolic control of smooth muscle cell phenotype switching in atherosclerosis.Science advances · 2026Article
- Decoding the Sex-Specific Architecture of Carotid Plaque Instability.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- Single-cell analysis of the progeria arterial wall reveals progerin-induced progressive, cell type-specific dysfunction and somatic mutation accumulation.Genome medicine · 2026Article
- Carotid plaque macrophage burden and inflammatory lipid-associated macrophage markers predict secondary major adverse cardiovascular events after endarterectomy.European heart journal · 2026Article
- Endothelial cannabinoid CB1 receptor deficiency reduces shear stress-induced arterial inflammation and lipid uptake.Nature communications · 2026Article
- Surgical Safety and Preservation of Quality of Life in Carotid Body Tumour Resection: The Role of Embolisation and Vulnerability Analysis in Working-Age Patients.Journal of clinical medicine · 2026Article
- Fibroblast-like cells accumulate late in human coronary atherosclerosis contributing to necrotic core formation.Cardiovascular research · 2026Article
- Endothelial to mesenchymal transition in cardiovascular diseases: molecular insights and clinical perspectives.European heart journal · 2026Review
- scSCCNIA: similarity matrix based contrastive clustering with neighbor information aggregation for single-cell RNA sequencing data.Briefings in bioinformatics · 2026Article
- Sex differences in endothelial cell biology: cellular phenotypes and molecular regulators.Frontiers in physiology · 2026Review
- Spatio-temporal dynamics of autophagy-associated genes in macrophage-driven atherosclerosis: an integrated omics and experimental study.Frontiers in endocrinology · 2026Article
- Toward Precision Medicine in Atherosclerotic Cardiovascular Disease: Insights from Omics Data into Sex Differences.Current atherosclerosis reports · 2025Review
- Single-Cell Transcriptomics Shows Cellular Heterogeneity, Intercellular Communication, and Extracellular Matrix Remodeling in Corneal Fibrosis In Vivo.Investigative ophthalmology & visual science · 2025Article
- Bottlenecks in advancing and applying multiomic data integration-common data resources as rate-limiting drivers-the high-impact use case of atherosclerotic cardiovascular disease.Briefings in bioinformatics · 2025Review
- Development and validation of a machine learning model for predicting vulnerable carotid plaques using routine blood biomarkers and derived indicators: insights into sex-related risk patterns.Cardiovascular diabetology · 2025Article
- Sex and the Garden of Eden.Nature cardiovascular research · 2025Article
Corrections and comments
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Authors and funding
29 authors.
Katyayani SukhavasiDepartment of Cardiac Surgery and The Heart Clinic, Tartu University Hospital and Department of Cardiology, Institute of Clinical Medicine, Tartu University, Tartu, Estonia. katyayani.sukhavasi@gmail.com.ORCID http://orcid.org/0000-0001-5627-0163
Giuseppe MocciDepartment of Medicine, Karolinska Institutet, Karolinska Universitetssjukhuset, Huddinge, Sweden.
Lijiang MaDepartment of Genetics and Genomic Sciences, Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Chani J HodonskyRobert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, VA, USA.ORCID http://orcid.org/0000-0001-8566-5877
Ernest Diez BenevanteLaboratory of Experimental Cardiology, Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.ORCID http://orcid.org/0000-0002-4313-4290
Lars MuhlDepartment of Medicine, Karolinska Institutet, Karolinska Universitetssjukhuset, Huddinge, Sweden.ORCID http://orcid.org/0000-0003-0952-0507
Jianping LiuDepartment of Medicine, Karolinska Institutet, Karolinska Universitetssjukhuset, Huddinge, Sweden.ORCID http://orcid.org/0000-0002-7336-3895
Sonja GustafssonDepartment of Medicine, Karolinska Institutet, Karolinska Universitetssjukhuset, Huddinge, Sweden.
Byambajav BuyandelgerDepartment of Medicine, Karolinska Institutet, Karolinska Universitetssjukhuset, Huddinge, Sweden.
Simon KoplevCancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0000-0002-8586-5614
Urban LendahlDepartment of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.
Michael VanlandewijckDepartment of Medicine, Karolinska Institutet, Karolinska Universitetssjukhuset, Huddinge, Sweden.
Prosanta SinghaA. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
Tiit ÖrdA. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
Mustafa BeterA. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.ORCID http://orcid.org/0000-0002-9497-3414
Ilakya SelvarajanA. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
Johanna P LaakkonenA. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
Marika VäliDepartment of Pathological Anatomy and Forensic Sciences, Tartu University, Tartu, Estonia.
Hester M den RuijterLaboratory of Experimental Cardiology, Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
Mete CivelekDepartment of Genome Sciences, University of Virginia, Charlottesville, VA, USA.ORCID http://orcid.org/0000-0002-8141-0284
Ke HaoDepartment of Genetics and Genomic Sciences, Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID http://orcid.org/0000-0002-1815-9197
Arno RuusaleppDepartment of Cardiac Surgery and The Heart Clinic, Tartu University Hospital and Department of Cardiology, Institute of Clinical Medicine, Tartu University, Tartu, Estonia.
Christer BetsholtzDepartment of Medicine, Karolinska Institutet, Karolinska Universitetssjukhuset, Huddinge, Sweden.
Heli JärveDepartment of Vascular Surgery and The Surgery Clinic, Tartu University Hospital, Tartu, Estonia.
Jason C KovacicCardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Clint L MillerRobert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, VA, USA.ORCID http://orcid.org/0000-0003-4276-3607
Casey RomanoskiDepartment of Cellular and Molecular Medicine, College of Medicine, University of Arizona, Tucson, AZ, USA.
Minna U KaikkonenA. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.ORCID http://orcid.org/0000-0001-6294-0979
Johan L M BjörkegrenDepartment of Medicine, Karolinska Institutet, Karolinska Universitetssjukhuset, Huddinge, Sweden. Johan.Bjorkegren@ki.se.ORCID http://orcid.org/0000-0003-1945-7425
Funding
Multimodal genetic regulatory architecture of coronary artery diseaseR01HL148239 · NHLBI · UNIVERSITY OF VIRGINIA · PI Clint L Miller · 2019 to 2026
$4.2MIntegrative genomic and functional genomic studies to connect variant to function for CAD GWAS lociR01HL168174 · NHLBI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Wei Li, EDOARDO MARCORA · 2023 to 2026
$3.1MUnderstanding the Molecular Mechanisms of Fibromuscular DysplasiaR01HL148167 · NHLBI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI KADIAN-DODOV, DANIELLA, KOVACIC, JASON CIRIL · 2020 to 2023
$2.8MBridgePRS: bridging the gap in polygenic risk scores between ancestries.R01HG012773 · NHGRI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Paul Francis O'Reilly · 2023 to 2026
$2.6MSystems Genetics of Vascular Smooth Muscle PhenotypesR01HL166428 · NHLBI · UNIVERSITY OF VIRGINIA · PI Mete Civelek · 2023 to 2026
$2.4MFunctional genomics investigation of pleiotropic vascular disease lociR01HL164577 · NHLBI · UNIVERSITY OF VIRGINIA · PI MILLER, CLINT L · 2022 to 2025
$2.3MMechanisms of ERG in Endothelial ActivationR01HL147187 · NHLBI · UNIVERSITY OF ARIZONA · PI ROMANOSKI, CASEY E · 2019 to 2023
$1.9MAmerican Heart Association (American Heart Association, Inc.) 19TPA34910021Fondation Leducq AtheroGen (22CVD04) and PlaqOmics(18CVD02)Fondation Leducq PlaqOmics (18CVD02)NHGRI NIH HHS R01 HG012773NHLBI NIH HHS R01 HL147187NHLBI NIH HHS R01 HL148167NHLBI NIH HHS R01 HL148239NHLBI NIH HHS R01 HL164577NHLBI NIH HHS R01 HL166428NHLBI NIH HHS R01 HL168174
Abstract
Carotid stenosis causes ischemic stroke in both sexes, but the clinical presentation and plaque characteristics differ. Here we run deep single-cell sequencing of 7,690 human carotid plaque cells from male and female patients. While we found no sex differences in major cell types, we identified a predominance of the osteogenic phenotype in smooth muscle cells, immunomodulating macrophages (MPs) and endothelial cells (ECs) undergoing endothelial-to-mesenchymal transition in females. In males, we found smooth muscle cells with the chondrocytic phenotype, MPs involved in tissue remodeling and ECs with angiogenic activity. Sex-biased subcellular clusters were integrated with tissue-specific gene-regulatory networks (GRNs) from the Stockholm-Tartu Atherosclerosis Reverse Network Engineering Task study. We identified GRN195 involved in angiogenesis and T cell-mediated cytotoxicity in male ECs, while in females, we found GRN33 and GRN122 related to TREM2
Indexed as
Carotid ArteriesCarotid StenosisEndothelial CellsGene Regulatory NetworksMyocytes, Smooth MusclePlaque, AtheroscleroticRNA-SeqSingle-Cell AnalysisTranscriptomeAgedCell ProliferationFemaleHumansMacrophagesMaleMiddle Aged
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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.