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Circ Res. 2019 Jul 19;125(3):356-366. doi: 10.1161/CIRCRESAHA.119.315054. Epub 2019 Jun 26.

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

Author information

1
From the Ludwig Boltzmann Institute for Lung Vascular Research, Medical University of Graz, Austria (G.K.).
2
Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, OH (A.K.Z.J.).
3
Division of Pulmonary and Critical Care Medicine, University of Cincinnati College of Medicine, OH (J.G.-A.).
4
Division of Pulmonary Biology, Perinatal Institute of Cincinnati Children's Hospital Research Foundation, OH (J.G.-A.).
5
Department of Pulmonary Medicine, Amsterdam University Medical Centers, the Netherlands (N.F.V.).

Abstract

RATIONALE:

CYPs (cytochrome p450) are critically involved in the metabolism of xenobiotics and toxins. Given that pulmonary hypertension is strongly associated with environmental exposure, we hypothesize 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 Medline (PubMed) database, as well as http://www.clinicaltrials.gov, for CYPs associated with many key aspects of pulmonary arterial hypertension including, but not limited to, severe pulmonary hypertension, estrogen metabolism, inflammation mechanisms, quasi-malignant cell growth, drug susceptibility, and metabolism of the pulmonary arterial hypertension-specific drugs.

CONCLUSIONS:

We postulate a hypothesis where the AhR (aryl hydrocarbon receptor) mediates aberrant cell growth via expression of different CYPs associated with estrogen metabolism and inflammation.

KEYWORDS:

environmental exposure; estrogens; inflammation; kynurenine; lung; vascular remodeling

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