Three‐dimensional Characterization of Occlusive Lesions in Pulmonary Arterial Hypertension

Abstract

Pulmonary arterial hypertension (PAH) includes a vasculopathy of fixed occlusive lesions in small pulmonary arteries. Evaluation of vascular lesions in PAH has relied on two‐dimensional histological preparations and morphological grading methodologies to evaluate lesion incidence and severity. However, this approach fails to acknowledge the structure of vascular lesions in situ and is inherently prone to investigator bias, leading to controversy regarding the hemodynamic impact of occlusive lesions in PAH and the possible misidentification of lesions within the lung vasculature. Therefore, we developed a semi‐automated, three‐dimensional approach to the analysis of composite serial histological sections to examine the geometry of vascular lesions in PAH. Given that recent studies of vascular morphology in PAH demonstrate that the progression of occlusive lesions has both temporal and spatial components, we tested the hypothesis that occlusive lesions within pulmonary arteries in PAH vary in composition and severity along the length of vessel segments. Using Sugen/hypoxia treated PAH rats, we found that lesion composition and severity was a complex function of vessel length, where von Willebrand factor‐positive endothelium and luminal occlusion surrounding plexiform lesion sites formed a highly variable continuum. These results suggest that the contribution of occlusive lesions to the pathophysiology of PAH may be misrepresented, and underscore the necessity of an unbiased approach to the anatomical characterization of the vasculopathy of PAH.Support or Funding InformationSupported by NIH HL66299 and HL60024.