ArticleNature medicine2015
KLF4-dependent phenotypic modulation of smooth muscle cells has a key role in atherosclerotic plaque pathogenesis.
Article in Nature medicine, 2015. 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 768 papers, 1 of them a synthesis that pooled 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.
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.
Who cites it
768 citing papers in PubMed, 1 synthesis or guideline pooled it, 1,172 citations in OpenAlex.
- Comprehensive Integration of Multiple Single-Cell Transcriptomic Data Sets Defines Distinct Cell Populations and Their Phenotypic Changes in Murine Atherosclerosis.Arteriosclerosis, thrombosis, and vascular biology · 2024Pooled it
- Intracranial aneurysms as a manifestation of premature vascular aging: Cellular senescence, inflammaging, and wall degeneration.Ageing research reviews · 2026Review
- Mechanosensitive Stanniocalcin-1 Suppresses Smooth Muscle Cell Proliferation and Attenuates Experimental Pulmonary Hypertension.Circulation research · 2026Article
- ATP Inside and Out: Understanding Atherosclerosis Through Energy Metabolism and Purinergic Signaling.Journal of atherosclerosis and thrombosis · 2026Review
- Article
- 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
- Smooth Muscle Cell Plasticity as a Central Determinant of Plaque Stability.Current atherosclerosis reports · 2026Review
- Atherosclerotic Cell Fates: A Single-Cell View of ER Stress.Journal of cardiovascular development and disease · 2026Review
- Maternal methionine supplementation regulates skeletal muscle development through NAnimal nutrition (Zhongguo xu mu shou yi xue hui) · 2026Article
- Olfactomedin-2 at the Crossroads of Smooth Muscle Cell Plasticity.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- A Rosella-PLIN2 knock-in mouse reveals lipophagy and immunometabolic interplay in atherosclerosis.Autophagy · 2026Article
- Dual Lineage Tracing Identifies Cellular Mechanisms Underlying Radiation-Associated Changes in Atherosclerotic Lesion Composition-Brief Report.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- Olfactomedin 2 Promotes Atherosclerosis by Eliciting Smooth Muscle Foam Cell Formation.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- Metabolic control of smooth muscle cell phenotype switching in atherosclerosis.Science advances · 2026Article
- Leiomodin 1 deficiency promotes lipid accumulation and redirects gene regulatory programs in smooth muscle cells exposed to oxidized LDL.Research square · 2026Article
- Mitochondrial Redox Failure Links Senescence-like Foam Cell Stress to Ferroptosis and Plaque Non-Resolution in Atherosclerosis.Antioxidants (Basel, Switzerland) · 2026Review
- Review
- Neuro-Mechanical Regulation of Vascular Smooth Muscle Cell Behaviour Under Ageing-Associated Substrate Stiffness.Current issues in molecular biology · 2026Article
- Transcriptomic, Specific Marker, and Pathway Analysis of Smooth Muscle Cell Foam Cells Relative to Macrophage Foam Cells in Human Atherosclerosis.bioRxiv : the preprint server for biology · 2026Article
- The Statin Floor Effect: a Mechanistic Framework for Residual Cardiovascular Risk.Cardiovascular drugs and therapy · 2026Review
708 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
Previous studies investigating the role of smooth muscle cells (SMCs) and macrophages in the pathogenesis of atherosclerosis have provided controversial results owing to the use of unreliable methods for clearly identifying each of these cell types. Here, using Myh11-CreER(T2) ROSA floxed STOP eYFP Apoe(-/-) mice to perform SMC lineage tracing, we find that traditional methods for detecting SMCs based on immunostaining for SMC markers fail to detect >80% of SMC-derived cells within advanced atherosclerotic lesions. These unidentified SMC-derived cells exhibit phenotypes of other cell lineages, including macrophages and mesenchymal stem cells (MSCs). SMC-specific conditional knockout of Krüppel-like factor 4 (Klf4) resulted in reduced numbers of SMC-derived MSC- and macrophage-like cells, a marked reduction in lesion size, and increases in multiple indices of plaque stability, including an increase in fibrous cap thickness as compared to wild-type controls. On the basis of in vivo KLF4 chromatin immunoprecipitation-sequencing (ChIP-seq) analyses and studies of cholesterol-treated cultured SMCs, we identified >800 KLF4 target genes, including many that regulate pro-inflammatory responses of SMCs. Our findings indicate that the contribution of SMCs to atherosclerotic plaques has been greatly underestimated, and that KLF4-dependent transitions in SMC phenotype are critical in lesion pathogenesis.
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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.