Baseline state for pulmonary vasculature with pulmonary arterial hypertension: effect of geometric remodeling and metabolic shift

Abstract Pulmonary arterial hypertension (PAH) is a complex disease characterized by chronically elevated pulmonary arterial pressure, with early onset and progression linked to structural, metabolic, and morphological changes in the pulmonary vasculature. Understanding the interplay between hemodynamics and arterial wall mechanics is essential to capture the pathology of the distal vasculature in PAH. This study aims to develop a data-driven framework that establishes a baseline state of PAH vasculature, incorporating key features of arterial wall constituents, geometry, and their interaction with PAH-specific hemodynamics. Illustrative examples of symmetrically bifurcating arterial trees are used to define representative baseline characteristics of PAH-affected pulmonary arteries. Compared with healthy homeostatic vasculature, the computational results demonstrate pronounced geometric and mechanical alterations: Arterial stiffness increases from approximately 7–10 kPa in healthy arteries to 300–800 kPa in PAH, representing a ~ 40–85 times increase across generations. Because wall thickening is imposed from histological measurements while outer diameter is preserved, the diameter-to-thickness ratio (D/h) decreases from ~ 14 in healthy arteries to ~ 3.8 in PAH, reflecting severe lumen narrowing and medial hypertrophy. In addition, the metabolic energy cost per unit length in PAH is more than double that of healthy arteries when assuming unchanged metabolic consumption per unit volume, whereas enforcing equal total energy cost yields a reduced per-volume metabolic consumption of ~ 450–500 W/m 3 . These findings suggest that maintaining constant metabolic consumption per unit volume would impose excessive energetic demand on the pulmonary vasculature in PAH, whereas redistribution of metabolic expenditure through altered wall composition may represent a more physiologically plausible adaptation. Furthermore, this framework provides a quantitative baseline state for PAH vasculature and lays the groundwork for future integration of growth-and-remodeling analyses and pharmacological pathway modeling to evaluate treatment response.