Single-Cell Analysis Reveals Distinct Immune and Smooth Muscle Cell Populations that Contribute to Chronic Thromboembolic Pulmonary Hypertension

Chronic thromboembolic pulmonary hypertension (CTEPH) occurs when a pulmonary embolism (PE) transforms into a chronic scar in the pulmonary arteries, resulting in vascular obstruction, microvasculopathy, and pulmonary hypertension. To better understand the pathobiology of CTEPH, researchers conducted single-cell RNA sequencing on tissue samples from CTEPH patients. They identified multiple cell types, including macrophages, T cells, and smooth muscle cells, within the CTEPH thrombus. Macrophages were found to promote pulmonary vascular remodeling through inflammatory signaling, while T cells contributed to chronic inflammation. Smooth muscle cells exhibited heterogeneity, including myofibroblasts associated with fibrosis. Moreover, the study identified a potential therapeutic target, protease-activated receptor 1 (PAR1), which when inhibited, decreased proliferation and migration of smooth muscle cells and myofibroblasts. These findings offer insights into CTEPH pathogenesis and propose new strategies for targeted treatments.