ArticleCirculation research2023
Proteomic Atlas of Atherosclerosis: The Contribution of Proteoglycans to Sex Differences, Plaque Phenotypes, and Outcomes.
Article in Circulation research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 2 of them syntheses that pooled it.
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Who cites it
59 citing papers in PubMed, 2 syntheses or guidelines pooled it, 69 citations in OpenAlex.
- 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
- Artificial intelligence in carotid research: a 25-year bibliometric analysis of global trends and future directions.Frontiers in artificial intelligence · 2026Pooled it
- Integrative Proteomic and Lipidomic Analysis of Patients With Acute Myocardial Infarction Treated With PCSK9 Antibodies and Statins.Circulation. Genomic and precision medicine · 2026Trial
- Quercetin Reduces Vascular Senescence and Inflammation in Symptomatic Male but Not Female Coronary Artery Disease Patients.Aging cell · 2025Trial
- Microbial metabolite-driven mechanisms linking the gut microbiome to atherosclerosis: multi-omic and translational perspectives.Gut microbes · 2026Review
- Post‑translational modifications in atherosclerosis: Roles, mechanisms and therapeutic potential (Review).International journal of molecular medicine · 2026Review
- Multimodal profiling of atherosclerosis: Protocol and pilot data for the AtherOMICS biobank.Science advances · 2026Article
- Aortic Stenosis Hyalectan Remodeling Revealed by Proteomics and Glycoproteomics.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- A Proteomic Atlas of Human Milk: Uncovering Milk Functional Components.Research square · 2026Article
- Gene expression profiles of carotid plaques differ between patients with amaurosis fugax and those with cerebral transient ischaemic attack or stroke.Cardiovascular research · 2026Article
- Spatial transcriptomics reveals a key role of fibroblast-like vascular smooth muscle cells in human atherosclerotic cell crosstalk and stability.European heart journal · 2026Article
- Molecular mechanism leading to human coronary atherosclerosis assessed by proteomic analysis and RNA sequences.European heart journal · 2026Article
- Sex differences in cardiovascular‑kidney‑metabolic syndrome: From pathogenesis to treatment response (Review).International journal of molecular medicine · 2026Review
- Proteomics reveals spatial and molecular heterogeneities in advanced atherosclerotic carotid artery plaques.Nature cardiovascular research · 2026Article
- A foam cell-targeted lipophagy restoration strategy stabilizes vulnerable atherosclerotic plaques.Bioactive materials · 2026Article
- Macrophage EHD1 Promotes Inflammation and Stabilizes Sortilin to Accelerate Atherosclerosis.Circulation research · 2026Article
- Single-cell T-cell landscape in atherosclerosis: implications for targeted therapy and beyond.Journal of translational medicine · 2026Review
- Consensus statement on mass spectrometry-based proteomic analysis of cardiac tissue.Nature cardiovascular research · 2026Article
- Unraveling Atherosclerosis through Multi-omics: Systematic Insights into the Unique Applications and Clinical Perspectives.Current atherosclerosis reports · 2026Review
- Single-nucleus RNA sequencing reveals the cellular composition and the mechanism underlying adrenal myelolipoma.Endocrine · 2026Article
Corrections and comments
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Authors and funding
25 authors at 5 institutions in 4 countries.
Funding
Abstract
backgroundUsing proteomics, we aimed to reveal molecular types of human atherosclerotic lesions and study their associations with histology, imaging, and cardiovascular outcomes.
methodsTwo hundred nineteen carotid endarterectomy samples were procured from 120 patients. A sequential protein extraction protocol was employed in conjunction with multiplexed, discovery proteomics. To focus on extracellular proteins, parallel reaction monitoring was employed for targeted proteomics. Proteomic signatures were integrated with bulk, single-cell, and spatial RNA-sequencing data, and validated in 200 patients from the Athero-Express Biobank study.
resultsThis extensive proteomics analysis identified plaque inflammation and calcification signatures, which were inversely correlated and validated using targeted proteomics. The inflammation signature was characterized by the presence of neutrophil-derived proteins, such as S100A8/9 (calprotectin) and myeloperoxidase, whereas the calcification signature included fetuin-A, osteopontin, and gamma-carboxylated proteins. The proteomics data also revealed sex differences in atherosclerosis, with large-aggregating proteoglycans versican and aggrecan being more abundant in females and exhibiting an inverse correlation with estradiol levels. The integration of RNA-sequencing data attributed the inflammation signature predominantly to neutrophils and macrophages, and the calcification and sex signatures to smooth muscle cells, except for certain plasma proteins that were not expressed but retained in plaques, such as fetuin-A. Dimensionality reduction and machine learning techniques were applied to identify 4 distinct plaque phenotypes based on proteomics data. A protein signature of 4 key proteins (calponin, protein C, serpin H1, and versican) predicted future cardiovascular mortality with an area under the curve of 75% and 67.5% in the discovery and validation cohort, respectively, surpassing the prognostic performance of imaging and histology.
conclusionsPlaque proteomics redefined clinically relevant patient groups with distinct outcomes, identifying subgroups of male and female patients with elevated risk of future cardiovascular events.
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Registered trials
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.