ArticlePLoS genetics2017
TCF21 and the environmental sensor aryl-hydrocarbon receptor cooperate to activate a pro-inflammatory gene expression program in coronary artery smooth muscle cells.
Article in PLoS genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.
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Who cites it
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 76 citations in OpenAlex.
- Exploring associations between estrogen and gene candidates identified by coronary artery disease genome-wide association studies.Frontiers in cardiovascular medicine · 2025Pooled it
- Vascular smooth muscle cell state trajectories mediate molecular mechanisms of coronary disease risk.Nature communications · 2026Article
- Decreased concentration of transcription factor 21 in patients with chronic schizophrenia is associated with an increased coronary artery calcium score.BMC psychiatry · 2026Article
- TCF21 promotes epithelial-to-mesenchymal transition and cytoskeleton reorganization in uterine development and endometriosis.Nature communications · 2026Article
- A cell and transcriptome atlas of human arterial vasculature.Cell genomics · 2025Article
- Enhancer-targeting CRISPR screens at coronary artery disease loci suggest shared mechanisms of disease risk.medRxiv : the preprint server for health sciences · 2025Article
- Environmental pollutants and atherosclerosis: Epigenetic mechanisms linking genetic risk and disease.Atherosclerosis · 2025Review
- Transcription Factor 21 Regulates Cardiac Myofibroblast Formation and Fibrosis.Circulation research · 2025Article
- Kynurenic Acid/AhR Signaling at the Junction of Inflammation and Cardiovascular Diseases.International journal of molecular sciences · 2024Review
- Associations of Long-Term Exposure to Fine Particulate Constituents With Cardiovascular Diseases and Underlying Metabolic Mediations: A Prospective Population-Based Cohort in Southwest China.Journal of the American Heart Association · 2024Article
- Thrombospondin-1 Drives Cardiac Remodeling in Chronic Kidney Disease.JACC. Basic to translational science · 2024Article
- Aryl hydrocarbon receptor: current perspectives on key signaling partners and immunoregulatory role in inflammatory diseases.Frontiers in immunology · 2024Review
- Article
- Integrated omics analysis of coronary artery calcifications and myocardial infarction: the Framingham Heart Study.Scientific reports · 2023Article
- Transcription factor 21 accelerates vascular calcification in mice by activating the IL-6/STAT3 signaling pathway and the interplay between VSMCs and ECs.Acta pharmacologica Sinica · 2023Article
- Bilirubin and Redox Stress in Age-Related Brain Diseases.Antioxidants (Basel, Switzerland) · 2023Review
- Dynamic changes in chromatin accessibility are associated with the atherogenic transitioning of vascular smooth muscle cells.Cardiovascular research · 2022Article
- Review
- Smad3 regulates smooth muscle cell fate and mediates adverse remodeling and calcification of the atherosclerotic plaque.Nature cardiovascular research · 2022Article
- Recent Major Transcriptomics and Epitranscriptomics Contributions toward Personalized and Precision Medicine.Journal of personalized medicine · 2022Review
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
Both environmental factors and genetic loci have been associated with coronary artery disease (CAD), however gene-gene and gene-environment interactions that might identify molecular mechanisms of risk are not easily studied by human genetic approaches. We have previously identified the transcription factor TCF21 as the causal CAD gene at 6q23.2 and characterized its downstream transcriptional network that is enriched for CAD GWAS genes. Here we investigate the hypothesis that TCF21 interacts with a downstream target gene, the aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor that mediates the cellular response to environmental contaminants, including dioxin and polycyclic aromatic hydrocarbons (e.g., tobacco smoke). Perturbation of TCF21 expression in human coronary artery smooth muscle cells (HCASMC) revealed that TCF21 promotes expression of AHR, its heterodimerization partner ARNT, and cooperates with these factors to upregulate a number of inflammatory downstream disease related genes including IL1A, MMP1, and CYP1A1. TCF21 was shown to bind in AHR, ARNT and downstream target gene loci, and co-localization was noted for AHR-ARNT and TCF21 binding sites genome-wide in regions of HCASMC open chromatin. These regions of co-localization were found to be enriched for GWAS signals associated with cardio-metabolic as well as chronic inflammatory disease phenotypes. Finally, we show that similar to TCF21, AHR gene expression is increased in atherosclerotic lesions in mice in vivo using laser capture microdissection, and AHR protein is localized in human carotid atherosclerotic lesions where it is associated with protein kinases with a critical role in innate immune response. These data suggest that TCF21 can cooperate with AHR to activate an inflammatory gene expression program that is exacerbated by environmental stimuli, and may contribute to the overall risk for CAD.
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