MITOCHONDRIAL DYSFUNCTION IN CHRONIC THROMBOEMBOLIC PULMONARY HYPERTENSION

Background and objectives: Pulmonary endarterectomy (PEA) is the treatment of choice for chronic thromboembolic pulmonary hypertension (CTEPH, ORPHA70591). The material obtained from PEA offers the unique opportunity to study the pathophysiological mechanisms of CTEPH at disease site. Hyperproliferative resistant phenotype of patient’s cells may suggest mitochondrial disarrangements which could explain CTEPH etiopathogenesis. We aimed to develop an in vitro model of CTEPH using patient-derived cell lines and to assess potential mitochondrial disturbances. Methods: PEA-obtained endothelial cells were characterized. We measured: i) Mitochondrial membrane potential (MMP), mitochondrial content and apoptosis/necrosis by flow cytometry and ii) mitochondrial dynamics (MD) by confocal microscopy. Results: CEPTH cells tended to show lower rates of depolarized MMP (49.91±14.70 vs. 59.87±8.41, p=NS), a decrease of mitochondrial content (148.94±69.96 vs. 295.57±178.60, PNS) and lower levels of necrosis/apoptosis (23.57±8.03 vs. 29.33±5.94, p=NS). Mitochondria from CTEPH patients tended to be smaller and to show higher circularity (0.45±0.009 vs. 0.43±0.012, p=NS), with less branching (2.77±0.14 vs. 2.93±0.06, p=NS) with respect to controls, both considered as pathologic markers. Conclusions: Mitochondrial changes are observed in patient-derived endothelial cells suggesting a potential etiopathogenic basis for CTEPH.