Mona Alotaibi, Lloyd D Harvey, William C Nichols, Michael W Pauciulo, Anna Hemnes, Tao Long, Jeramie D Watrous, Arjana Begzati, Jaakko Tuomilehto, Aki S Havulinna, Teemu J Niiranen, Pekka Jousilahti, Veikko Salomaa, Thomas Bertero, Nick H Kim, Ankit A Desai, Atul Malhotra, Jason X-J Yuan, Susan Cheng, Stephen Y Chan, Mohit Jain
Pulmonary arterial hypertension (PAH) is a rare and fatal vascular disease with heterogeneous clinical manifestations. To date, molecular determinants underlying the development of PAH and related outcomes remain poorly understood. Herein, we identify pulmonary primary oxysterol and bile acid synthesis (PPOBAS) as a previously unrecognized pathway central to PAH pathophysiology. Mass spectrometry analysis of 2,756 individuals across five independent studies revealed 51 distinct circulating metabolites that predicted PAH-related mortality and were enriched within the PPOBAS pathway...
January 23, 2024: bioRxiv