Individualized Interactomes From Pulmonary Arterial Hypertension Cell Biopsies Inform Pharmacotherapeutic Response

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.