The Role of Aryl Hydrocarbon Receptor in the Pathogenesis of Cardiovascular Diseases

@article{Korashy2006TheRO,
  title={The Role of Aryl Hydrocarbon Receptor in the Pathogenesis of Cardiovascular Diseases},
  author={Hesham M. Korashy and Ayman O. S. El-Kadi},
  journal={Drug Metabolism Reviews},
  year={2006},
  volume={38},
  pages={411 - 450}
}
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… 

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References

SHOWING 1-10 OF 217 REFERENCES

A possible mechanism for atherosclerosis induced by polycyclic aromatic hydrocarbons.

CYP1A1-mediated mechanism for atherosclerosis induced by polycyclic aromatic hydrocarbons.

The aryl hydrocarbon receptor: a comparative perspective.

  • M. E. Hahn
  • Biology, Chemistry
    Comparative biochemistry and physiology. Part C, Pharmacology, toxicology & endocrinology
  • 1998

Ah receptor signaling pathways.

TLDR
The objective is to review the Ah receptor's role in regulation of xenobiotic metabolism and use this model as a framework for understanding the less well-characterized mechanism of dioxin toxicity.

The aryl hydrocarbon receptor and its xenobiotic ligands: a fundamental trigger for cardiovascular diseases.

A role for the aryl hydrocarbon receptor in cardiac physiology and function as demonstrated by AhR knockout mice

TLDR
The anatomic remodeling without typical features of molecular remodeling is not consistent with hypertrophic growth secondary to pressure or volume overload, suggesting that increased cardiomyocyte size may be a direct consequence of the absence of the AhR in this cell type.

Induction of cytochrome CYPIA1 and formation of toxic metabolites of benzo[a]pyrene by rat aorta: a possible role in atherogenesis.

TLDR
The data suggest that the aortas of induced animals metabolize the BaP in cigarette smoke to carcinogenic and toxic products and that this metabolism may initiate vessel injury and lead to the accelerated atherosclerosis seen in cigarette smokers.

Tissue distribution and function of the Aryl hydrocarbon receptor repressor (AhRR) in C57BL/6 and Aryl hydrocarbon receptor deficient mice

TLDR
Tissue distribution of AhRR in AhR deficient and wild type C57BL/6 mice is reported and simultaneous measurements of CYP1A1 and AhRR mRNA expression do not strongly support the view that the AhRR tissue pattern triggers the tissue specific responsiveness of AhR-regulated genes to B(a)P treatment.
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