Resident cell lineages are preserved in pulmonary vascular remodeling

Abstract Pulmonary vascular remodeling is the main pathological hallmark of pulmonary hypertension disease. We undertook a comprehensive and multilevel approach to investigate the origin of smooth muscle actin‐expressing cells in remodeled vessels. Transgenic mice that allow for specific, inducible and permanent labeling of endothelial (Cdh5‐tdTomato), smooth muscle (Acta2‐, Myh11‐tdTomato), pericyte (Cspg4‐tdTomato) and fibroblast (Pdgfra‐tdTomato) lineages were used to delineate the cellular origins of pulmonary vascular remodeling. Mapping the fate of major lung resident cell types revealed smooth muscle cells (SMC) as the predominant source of cells that populate remodeled pulmonary vessels in chronic hypoxia and allergen‐induced murine models. Combining in vivo cell type‐specific, time‐controlled labeling of proliferating cells with a pulmonary artery phenotypic explant assay, we identified proliferation of SMC as an underlying remodeling pathomechanism. Multi‐color immunofluorescence analysis showed a preserved pattern of cell type marker localization in murine and human pulmonary arteries, in both donors and idiopathic pulmonary arterial hypertension patients (IPAH). Whilst neural glial antigen 2 (chondroitin sulphate proteoglycan 4) labeled mostly vascular supportive cells with partial overlap with SMC markers, PDGFRα‐expressing cells were observed in the perivascular compartment. The luminal vessel side was lined by a single cell layer expressi...
Source: The Journal of Pathology - Category: Pathology Authors: Tags: Original Paper Source Type: research