Resident cell lineages are preserved in pulmonary vascular remodeling.

摘要: Pulmonary vascular remodeling is the main pathological hallmark of pulmonary hypertension disease. We undertook a comprehensive and multilevel approach to investigate origin smooth muscle actin-expressing cells in remodeled vessels. Transgenic mice that allow for specific, inducible, permanent labeling endothelial (Cdh5-tdTomato), (Acta2-, Myh11-tdTomato), pericyte (Cspg4-tdTomato), fibroblast (Pdgfra-tdTomato) lineages were used delineate cellular origins remodeling. Mapping fate major lung resident cell types revealed (SMCs) as predominant source populate vessels chronic hypoxia allergen-induced murine models. Combining vivo type-specific, time-controlled proliferating with artery phenotypic explant assay, we identified proliferation SMCs an underlying pathomechanism. Multicolor immunofluorescence analysis showed preserved pattern type marker localization human arteries, both donors idiopathic arterial (IPAH) patients. Whilst neural glial antigen 2 (chondroitin sulfate proteoglycan 4) labeled mostly supportive partial overlap SMC markers, PDGFRα-expressing observed perivascular compartment. The luminal vessel side was lined by single layer expressing markers followed adjacent distinct defined expression pronounced thickening Quantitative flow cytometric digests diverse layers separation into two discrete populations either (EC) or Additionally, found no evidence between EC ultrastructural characteristics using electron microscopy donor IPAH arteries. Lineage-specific profiles are retained during without any indication conversion. expansion evolutionarily conserved paradigm disease pathogenesis. © 2018 Authors. Journal Pathology published John Wiley & Sons Ltd on behalf Pathological Society Great Britain Ireland.