A Single-cell Census of Pulmonary Endarterectomies Tissue across different anatomical regions in chronic thromboembolic pulmonary hypertension

The operation of PEA surgery included removal of proximal thromboembolic materials and their secondary branches. Therefore, our study aims to identify the cellular landscape and pathological features across different anatomical regions. We use single-cell transcriptomics to profile the cellular composition of the main and their bifurcate portion within PEA tissues and healthy pulmonary arteries. The proportion of mononuclear phagocytes was significantly increased in the main portion. Meanwhile, inflammatory response and pro-inflammatory activity were attributed to CD8+ effector T cells and nature killer cells subsets and a M1-like phenotypic macrophage subcluster. While the colander-like lesions were dominant in the bifurcate portion, and the percentage of plasma cells was markedly increased. Differently, immune dysregulation was induced from naïve T cells, and an upregulation of plasminogen activator receptor promoted to macrophage infiltration into the vascular wall. Notably, a SMCs subcluster gained myofibroblast markers and was predicted to transition to myofibroblasts in the bifurcate portion. The regions with colander-like lesions changes had more obviously T cell and macrophages driving immune-inflammatory response and SMCs differentiation, suggesting removal of proximal occlusion without endarterectomy of all the distal branches would leave significant disease behind for CTEPH.