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

  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},
  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… 

Roles of xenobiotic receptors in vascular pathophysiology.

It is suggested that the functions of PXR, CAR and AhR may be closely implicated in the pathogeneses of metabolic vascular diseases, such as hyperlipidemia, atherogenesis, and hypertension and manipulation of the activities of these receptors may provide novel strategies for the treatment of vascular diseases.

Potential role of CYP1B1 in the development and treatment of metabolic diseases

Mitochondrial activity and oxidative stress functions are influenced by the activation of AhR-induced CYP1A1 overexpression in cardiomyocytes

Exposure to TCDD results in regulatory alteration to the expression of detoxification genes that ultimately affect the metabolic activation and function of cardiomyocytes, and may provide an explanation for myocardial injuries caused by polycyclic aromatic hydrocarbons.

Activation of the aryl hydrocarbon receptor by doxorubicin mediates cytoprotective effects in the heart.

It is shown that AhR plays an important role in DOX metabolism by the heart and is cardioprotective against DOX-induced cardiotoxicity, and these findings indicate that DOx-induced upregulation of CYP1A1 and GSTA1 expression is AhR dependent.

The role of mid-chain hydroxyeicosatetraenoic acids in the pathogenesis of hypertension and cardiac hypertrophy

A clear understanding is provided of the role of mid-chain HETEs in the pathogenesis of cardiovascular diseases and their importance as novel targets in the treatment for hypertension and cardiac hypertrophy.

CYP1B1 as a therapeutic target in cardio-oncology

There is growing body of evidence suggesting that inhibition of the cytochrome P450 1B1 enzyme (CYP1B1) can be a promising therapeutic strategy that has the potential to prevent cancer treatment-induced cardiovascular complications without reducing their anti-cancer effects.



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.

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

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.

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

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.