Kynurenine pathway metabolism evolves with development of preclinical and scleroderma-associated pulmonary arterial hypertension
Catherine E. Simpson, A.S. Ambade, Robert Harlan, Aurelie Roux, Susan Aja, David R. Graham, Ami A. Shah, Laura K. Hummers, Anna R. Hemnes, Jane A. Leopold, Evelyn M. Horn, Erika B. Rosenzweig, Gabriele Grünig, Micheala A. Aldred, John Barnard, Suzy Comhair, W.H. Wilson Tang, Megan Griffiths, Franz Rischard, Robert P. Frantz, Serpil C. Erzurum, Gerald J. Beck, Nicholas S. Hill, Stephen C. Mathai, Paul M. Hassoun, Rachel L. Damico, and the PVDOMICS Study Group
Abstract
Our study shows an early increase in kynurenine pathway metabolism in at-risk subjects with systemic sclerosis who develop pulmonary arterial hypertension (PAH). We show that kynurenine pathway upregulation precedes clinical diagnosis and that this metabolic shift is associated with increased disease severity and shorter survival times. We also show that gene expression of TDO2, an enzyme that generates kynurenine from tryptophan, rises with PAH development.