Abstract Body: Pulmonary arterial hypertension (PAH) is a progressive and fatal vascular disorder characterized by profound endothelial dysfunction, capillary rarefaction, and extensive remodeling of proximal pulmonary arteries. Despite accumulating evidence of endothelial heterogeneity from single-cell studies, the spatial microenvironmental drivers that govern capillary loss and arterial remodeling remain incompletely defined. In this study, we combined single-cell RNA sequencing with spatial transcriptomics to spatially map endothelial and stromal niches in pulmonary hypertension. Integration of datasets allowed systematic identification of spatial niches; mapping of ligand–receptor signaling using CellChat; and orthogonal validation using histology, immunofluorescence, and RNAscope. We discovered PH-specific vascular niches marked by a pronounced loss of the capillary–pericyte compartment and a corresponding enrichment of arterial fibrotic and inflammatory microenvironments. Disruption of capillary–pericyte interactions revealed several ligand–receptor pathways driving capillary dropout, including reduced VEGFA–KDR signaling. Spatial mapping also uncovered discrete proximal and distal arterial niches with distinct combinations of endothelial cells and fibroblast/immune cell partners: AECs interacting with AF2 fibroblasts and interstitial macrophages defined the proximal arterial niche, driven by profibrotic and inflammatory pathways, while distal arterial remodeling involved coordinated interactions among arterial ECs, AF1 fibroblasts, and alveolar macrophages. Together, these findings delineate spatially confined endothelial dysfunction associated with PH progression and highlight actionable molecular nodes—including aberrant Notch activation and loss of VEGFA signaling—that represent potential therapeutic targets.