Viewing Pulmonary Arterial Hypertension Pathogenesis and Opportunities for Disease-Modifying Therapy Through the Lens of Biomass

Abstract

Fibroproliferative remodeling of distal pulmonary arterioles is a cornerstone characteristic of pulmonary arterial hypertension (PAH). Data from contemporary quantitative imaging suggest that anabolic synthesis of macromolecular substrate, defined here as biomass, is the proximate event that causes vascular remodeling via pathogenic changes to DNA, collagen, cytoskeleton, and lipid membranes. Modifying biomass is achievable but requires tilting the balance in favor of endogenous degradation over synthetic pathways in order to advance the first-ever disease-modifying PAH pharmacotherapy. Viewing PAH pathobiology through the lens of biomass represents an opportunity to decipher novel determinants of disease inception and inform interventions that induce reverse remodeling.