The Role of Aryl Hydrocarbon Receptor in the Pathogenesis of Cardiovascular Diseases
Bibliographic record
Abstract
Numerous experimental and epidemiological studies have demonstrated that polycyclic aromatic hydrocarbons (PAHs), which are major constituents of cigarette tobacco tar, are strongly involved in the pathogenesis of the cardiovascular diseases (CVDs). Knowing that PAH-induced toxicities are mediated by the activation of a cytosolic receptor, aryl hydrocarbon receptor (AhR), which regulates the expression of a group of xenobiotic metabolizing enzymes (XMEs) such as CYP1A1, CYP1A2, CYP1B1, NQO1, and GSTA1, suggests a direct link between AhR-regulated XMEs and CVDs. Therefore, identifying the localization and expression of the AhR and its regulated XMEs in the cardiovascular system (CVS) is of major importance in understanding their physiological and pathological roles. Generally, it was believed that the levels of AhR-regulated XMEs are lower in the CVS than in the liver; however, it has been shown that similar or even higher levels of expression are demonstrated in the CVS in a tissue- and species-specific manner. Moreover, most, if not all, AhR-regulated XMEs are differentially expressed in most of the CVS, particularly in the endothelium cells, aorta, coronary arteries, and ventricles. Although the exact mechanisms of PAH-mediated cardiotoxicity are not fully understood, several mechanisms are proposed. Generally, induction of CYP1A1, CYP1A2, and CYP1B1 is considered cardiotoxic through generating reactive oxygen species (ROS), DNA adducts, and endogenous arachidonic acid metabolites. However the cardioprotective properties of NQO1 and GSTA1 are mainly attributed to the antioxidant effect by decreasing ROS and increasing the levels of endogenous antioxidants. This review provides a clear understanding of the role of AhR and its regulated XMEs in the pathogenesis of CVDs, in which imbalance in the expression of cardioprotective and cardiotoxic XMEs is the main determinant of PAH-mediated cardiotoxicity.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".