Rui-Sheng Wang, Navneet Singh, Henri Wathieu, Grayson Baird, Katherine Cox-Flaherty, James R Klinger, Christopher J Mullin, Mandy Pereira, Mary Whittenhall, Elizabeth O Harrington, Bradley A Maron, Corey E Ventetuolo
Pulmonary arterial hypertension (PAH) is characterized by molecular heterogeneity, which has limited personalized approaches to treatment selection. In this study, the authors assembled a novel pipeline that leveraged pulmonary artery endothelial cell biopsies acquired at the point of care to build individualized interactomes that served as the basis for a systems pharmacology analysis. Concordance between the molecular targets of a prescribed PAH pharmacotherapy class and interactome topology was associated with improved clinical outcomes using a retrospective in silico trial design. These data suggest that clinically actionable individualized treatment selection is feasible in PAH with relevance to other complex cardiovascular diseases.