Aryl-hydrocarbon receptor in smooth muscle cells protect against dioxin induced adverse remodeling of atherosclerosis
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View abstract on PubMed
Summary
This summary is machine-generated.Environmental dioxin exposure accelerates atherosclerosis by modulating smooth muscle cells (SMC). The Aryl-hydrocarbon receptor (AHR) in SMCs protects against dioxin
Area Of Science
- Cardiovascular Research
- Environmental Toxicology
- Cell Biology
Background
- Environmental dioxin exposure is linked to increased myocardial infarction risk.
- Smooth muscle cells (SMC) play a key role in atherosclerotic plaque remodeling.
- The precise mechanisms of dioxin's adverse effects on SMCs remain unclear.
Purpose Of The Study
- To elucidate the molecular mechanisms by which dioxin exposure modulates SMCs in atherosclerosis.
- To investigate the role of the Aryl-hydrocarbon receptor (AHR) in dioxin-induced SMC dysfunction.
- To determine how dioxin impacts atherosclerotic plaque development and stability.
Main Methods
- Single-cell RNA and ATAC sequencing on mouse aorta and primary human coronary artery SMCs exposed to 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD).
- Histological analyses, functional phenotypic assays, and ChIP-Sequencing for AHR and TCF21.
- SMC-specific <i>Ahr</i> knockout mouse models were utilized.
Main Results
- Dioxin exposure modulated SMCs, accelerating atherosclerosis by increasing lesion size, SMC migration, and macrophage recruitment.
- <i>C3</i>-expressing modulated SMCs were associated with increased inflammation.
- TCDD treatment altered gene expression and chromatin accessibility, enriching for AHR binding and decreasing TCF21 occupancy.
- SMC-specific <i>Ahr</i> knockout exacerbated dioxin-induced plaque vulnerability, oxidative stress, and macrophage infiltration.
Conclusions
- Dioxin adversely remodels atherosclerotic plaques by promoting SMC phenotypic modulation, inflammation, and oxidative stress.
- TCF21 occupancy may be a key factor in dioxin's adverse effects on SMC phenotype.
- AHR signaling in SMCs confers protection against dioxin-induced atherosclerosis by stabilizing plaque phenotype and reducing oxidative stress.
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