Comparison of metabolic profile in endothelial cells of chronic thromboembolic pulmonary hypertension and pulmonary arterial hypertension

Abstract

Background: Chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary arterial hypertension (PAH) are two subtypes of pulmonary hypertension (PH). Endothelial dysfunction is believed the main cause of the hyperproliferative and antiapoptotic phenotype in PH characterized by increased glycolysis in PAH. It is unknown whether PAH and CTEPH share the same metabolic abnormalities. The aim of our study is to perform a systematic metabolic comparison of endothelial cells (ECs) derived from PAH and CTEPH patients. Methods: ECs from human pulmonary artery endothelial cells HPAECs (n=3), CTEPH (n=7) and PAH (n=6) were expanded until the same passage. Metabolic targets were analysed by qRT-PCR and Western Blot. Viability and migration were studied using MTT and wound healing assay. Supernatants were assessed by BGEM Test Cards. All values are shown as mean±SD. The analysis was performed using one-way ANOVA (p Results: Gene and protein expression of key glycolytic enzymes were significantly upregulated in PAH-ECs compared to CTEPH-ECs and HPAECs. Mitochondrial enzymes, pentose phosphate pathway and glutamine metabolism-related enzymes were upregulated in PAH-ECs compared to the CTEPH-ECs and HPAECs. Both PAH and CTEPH-ECs showed significant higher viability compared to HPAECs. Acidification of the supernatant was detected in both patients’ lines. Statistical higher glucose and lower lactate concentration in the supernatant were shown in HPAECs compared to patient cell lines. Conclusion: PAH-ECs were found to be metabolically different than CTEPH-ECs indicating distinct pathogenic mechanisms in the development of the two PH subtypes. This creates the opportunity to specifically target the distinct metabolic abnormalities in both diseases.