The Role of the Aryl Hydrocarbon Receptor/ARNT/Cytochrome P450 System in Pulmonary Vascular Diseases- A Hypothesis.

RATIONALE CYPs are critically involved in the metabolism of xenobiotics and toxins. Given that pulmonary hypertension is strongly associated with environmental exposure, we hypothesizes that CYPs play a role in the development and maintenance of pathological vascular remodeling. OBJECTIVE We sought to identify key CYPs that could link drug or hormone metabolism to the development of pulmonary hypertension. METHODS AND RESULTS We searched in the Medline (PubMed) database, as well as clinicaltrials.gov for CYPs associated with many key aspects of pulmonary arterial hypertension including, but limited to, severe pulmonary hypertension, estrogen metabolism, inflammation mechanisms, quasi-malignant cell growth, drug susceptibility and metabolism of the PAH-specific drugs. CONCLUSIONS We postulate a hypothesis where the aryl-hydrocarbon receptor mediates aberrant cell growth via expression of different CYPs associated with estrogen metabolim and inflammation.

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