Grazyna Kwapiszewska1, Anne Katrine Z Johansen2, Jose Gomez-Arroyo3,4, Norbert F Voelkel5. 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.
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.
Authors: Steven M Kawut; Diane Pinder; Nadine Al-Naamani; Amber McCormick; Harold I Palevsky; Jason Fritz; K Akaya Smith; Jeremy A Mazurek; Margaret F Doyle; Margaret R MacLean; Angela DeMichele; David A Mankoff Journal: Ann Am Thorac Soc Date: 2019-11