The significance of CD16+ monocytes in the occurrence and development of chronic thromboembolic pulmonary hypertension: insights from single-cell RNA sequencing

<bold>Background:</bold> Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by pulmonary artery thrombi and microvascular remodeling. Its pathogenesis involves inflammation, immunity, coagulation, and angiogenesis. Monocytes, pivotal in thrombus formation, lack systematic study in CTEPH. This research, using single-cell sequencing, explores monocyte subsets in CTEPH, aiming to enhance understanding for diagnosis and treatment. <bold>Methods:</bold> Single-cell RNA sequencing analyzed PBMCs from healthy controls, CTEPH patients, and tissues from CTEPH patients after the pulmonary endarterectomy. We developed a CTEPH rat model by using autologous thrombi injection via a central venous catheter. Flow cytometry assessed monocyte subset changes in both patients and the rat model. Immunofluorescence staining observed macrophage subsets in thrombus tissue. <bold>Results:</bold> CD16+ monocyte subset increased significantly in CTEPH patients, with distinct transcriptomic features related to thrombus formation. Pro-inflammatory and lipid metabolism reprogramming occurred in macrophage subsets in pulmonary endarterectomy tissue of CTEPH patients. CD16+ monocytes in CTEPH patients migrated to thrombus and differentiated into IL-1β-expressing macrophages, contributing to disease progression. <bold>Conclusion:</bold> CD16+ monocytes undergo significant gene expression changes in CTEPH, impacting platelet activation, coagulation, and inflammation. Their migration to thrombus and differentiation into IL-1β-expressing macrophages suggest their crucial role in CTEPH pathogenesis, offering potential therapeutic targets.