ArticleEuropean heart journal2025
Atheroma transcriptomics identifies ARNTL as a smooth muscle cell regulator and with clinical and genetic data improves risk stratification.
Article in European heart journal, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- The changing epidemiology of human type 2 diabetes-associated atherosclerosis: Pathophysiological mechanisms and emerging treatment possibilities.Journal of internal medicine · 2026Review
- Inflammation in atherosclerosis: Drivers, mechanisms and therapies.Acta pharmaceutica Sinica. B · 2026Review
- Spatial transcriptomics reveals a key role of fibroblast-like vascular smooth muscle cells in human atherosclerotic cell crosstalk and stability.European heart journal · 2026Article
- Unraveling Atherosclerosis through Multi-omics: Systematic Insights into the Unique Applications and Clinical Perspectives.Current atherosclerosis reports · 2026Review
- Multiomics for Risk Stratification in Atherosclerotic Cardiovascular Disease.Circulation. Genomic and precision medicine · 2026Review
- Multi-omics data integration from patients with carotid stenosis illuminates key molecular signatures of atherosclerotic instability.Genome medicine · 2026Article
- A single-cell and spatial atlas of plaque macrophage states in human atherosclerosis.Frontiers in immunology · 2026Review
- Insulin use promotes pro-inflammatory changes in the transcriptome of atherosclerotic plaques in patients with diabetes mellitus.Journal of molecular and cellular cardiology plus · 2025Article
- Inflammation reprogramming and immunomodulation: Next-generation treatments for atherosclerosis.Cell reports. Medicine · 2025Review
- Dissecting the effect of genetic variants on atherosclerosis: integrating bulk and single-cell transcriptomics.European heart journal · 2025Article
Corrections and comments
- Erratum issued
Authors and funding
18 authors.
Funding
Abstract
BACKGROUND AND
aimsThe role of vascular smooth muscle cells (SMCs) in atherosclerosis has evolved to indicate causal genetic links with the disease. Single cell RNA sequencing (scRNAseq) studies have identified multiple cell populations of mesenchymal origin within atherosclerotic lesions, including various SMC sub-phenotypes, but it is unknown how they relate to patient clinical parameters and genetics. Here, mesenchymal cell populations in atherosclerotic plaques were correlated with major coronary artery disease (CAD) genetic variants and functional analyses performed to identify SMC markers involved in the disease.
methodsBioinformatic deconvolution was done on bulk microarrays from carotid plaques in the Biobank of Karolinska Endarterectomies (BiKE, n = 125) using public plaque scRNAseq data and associated with patient clinical data and follow-up information. BiKE patients were clustered based on the deconvoluted cell fractions. Quantitative trait loci (QTLs) analyses were performed to predict the effect of CAD associated genetic variants on mesenchymal cell fractions (cfQTLs) and gene expression (eQTLs) in plaques.
resultsLesions from symptomatic patients had higher fractions of Type 1 macrophages and pericytes, but lower fractions of classical and modulated SMCs compared with asymptomatic ones, particularly females. Presence of diabetes or statin treatment did not affect the cell fraction distribution. Clustering based on plaque cell fractions, revealed three patient groups, with relative differences in their stability profiles and associations to stroke, even during long-term follow-up. Several single nucleotide polymorphisms associated with plaque mesenchymal cell fractions, upstream of the circadian rhythm gene ARNTL were identified. In vitro silencing of ARNTL in human carotid SMCs increased the expression of contractile markers and attenuated cell proliferation.
conclusionsThis study shows the potential of combining scRNAseq data with vertically integrated clinical, genetic, and transcriptomic data from a large biobank of human plaques, for refinement of patient vulnerability and risk prediction stratification. The study revealed novel CAD-associated variants that may be functionally linked to SMCs in atherosclerotic plaques. Specifically, variants in the ARNTL gene may influence SMC ratios and function, and its role as a regulator of SMC proliferation should be further investigated.
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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 Socratic graph.