Abstract / Summary
Background: Pulmonary endarterectomy (PEA) remains one of potentially curative options for chronic thromboembolic pulmonary hypertension (CTEPH). The operation can remove proximal thromboembolic materials and their secondary branches. However, the cellular landscape and pathological features across different anatomical regions remain limited understood.
Methods: Ten patients with CTEPH undergoing PEA surgery and six reference distal pulmonary arteries were conducted single-cell transcriptomics to profile the cellular composition of the main and its bifurcate portion.
Results: Pronounced muscularised and fibrotic thrombi organisation were presented in the main portion, and the proportion of mononuclear phagocytes was significantly increased. Inflammatory response and pro-inflammatory activity were attributed to CD8+ effector T cells and nature killer cells subsets and a M1-like (high IL1B and TNF, minimal IL6) phenotypic macrophage subcluster. The colander-like lesions were dominant in the bifurcate portion, and the percentage of plasma cells was markedly increased. Immune dysregulation was induced from CD4 naïve T cells, and a downregulation of M2-like macrophage infiltration into the vascular wall. The expression of plasminogen activator, urokinase receptor, urokinase receptor (PLAUR; plasminogen activator) were observed in M2-like (high MRC1 and CD163, virtually no IL1B or TNF) macrophage in bifurcate portion. Notably, one of smooth muscle cells (SMCs) subclusters in the bifurcate portion gained more significantly myofibroblast markers than those in the main portion, and other subclusters remained the function of SMCs.
Conclusions: The regions with colander-like lesions changes had more obviously T cell and macrophages driving immune-inflammatory response and SMCs differentiation, suggesting that combining therapeutic interventions after surgical removal of accessible thrombus may be beneficial.
Key points: This study reveals the comprehensive cellular composition in main/lobar and bifurcate pulmonary endarterectomy (PEA) specimens at the single-cell level. The bifurcate regions with colander had more obviously T cell and macrophages driving immune-inflammatory response and smooth muscle cells (SMCs) differentiation, however, the remodelling of distal or micro-vessels still remained.