Comparative analysis of circulating endothelial progenitor cells and resected tissue-derived endothelial cells in chronic thromboembolic pulmonary hypertension (CTEPH).

Endothelial dysfunction (ED) is pivotal in Chronic Thromboembolic Pulmonary Hypertension (CTEPH) pathogenesis. While previous studies from our group have demonstrated phenotypic changes in endothelial cells (ECs) within the thromboembolic material, systemic implications of ED in CTEPH are poorly understood. This study investigates whether observed ED is confined to ECs derived from thromboembolic tissue (CTEPH-EC) or extends to circulating endothelial progenitor cells (CTEPH-ECFC). CTEPH-EC and CTEPH-ECFC were isolated from the same patient. Control samples were isolated from systemic circulation (CTL-ECFC) and pulmonary arteries (HPAE) of healthy individuals. Phenotype and functional assays were conducted. Both CTEPH-EC and CTEPH-ECFC showed lower proliferation rates compared to their controls, and impaired wound repair: CTEPH-EC (31.22%vs.73.97%,p<0.01), and CTEPH-ECFC (52.63%vs.94.24%,p<0.01). Angiogenic ability was also diminished in CTEPH-EC (54vs.171,p<0.05) and CTEPH-ECFC (103vs.159,p<0.05). Furthermore, both groups exhibited a higher degree of mitochondrial membrane polarization, indicated by JC-1 dye, CTEPH-EC (0.5383vs.1.319,p<0.05) and CTEPH-ECFC (0.2484vs.1.239,p<0.05). Senescence, quantified by β-galactosidase-positive cells was elevated in CTEPH-EC (17%vs.5%,p<0.01) and CTEPH-ECFC (14%vs.7%, p<0.05). Oxidative stress was also increased in both CTEPH-EC (20.28vs.13.35,p<0.05) and CTEPH-ECFC (22.50vs.6.75,p<0.01). Preliminary findings show systemic ED in in paired CTEPH-EC and CTEPH-ECFC samples, indicating that ED extends beyond affected tissue-derived ECs, impacting circulating ECs.