Journal Article

Metabolic profile in endothelial cells of chronic thromboembolic pulmonary hypertension and pulmonary arterial hypertension

Smolders, V. F. E. D., Sebastián, L., Bogaard, Harm Jan, Roger, Y., Bonjoch, C., Osorio, J., Morén, Constanza, Blanco, I., Cascante, M., Tura-Ceide, O., Hu, X., Peinado, V. I., Piccari, L., Quax, P. H. A., Barberà, J. A., Szulcek, R., Castellà, M., Rodríguez, C., Timens, Wim

2022

Overview

Chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary arterial hypertension (PAH) are two forms of pulmonary hypertension (PH) characterized by obstructive vasculopathy. Endothelial dysfunction along with metabolic changes towards increased glycolysis are important in PAH pathophysiology. Less is known about such abnormalities in endothelial cells (ECs) from CTEPH patients. This study provides a systematic metabolic comparison of ECs derived from CTEPH and PAH patients. Metabolic gene expression was studied using qPCR in cultured CTEPH-EC and PAH-EC. Western blot analyses were done for HK2, LDHA, PDHA1, PDK and G6PD. Basal viability of CTEPH-EC and PAH-EC with the incubation with metabolic inhibitors was measured using colorimetric viability assays. Human pulmonary artery endothelial cells (HPAEC) were used as healthy controls. Whereas PAH-EC showed significant higher mRNA levels of GLUT1, HK2, LDHA, PDHA1 and GLUD1 metabolic enzymes compared to HPAEC, CTEPH-EC did not. Oxidative phosphorylation associated proteins had an increased expression in PAH-EC compared to CTEPH-EC and HPAEC. PAH-EC, CTEPH-EC and HPAEC presented similar HOXD macrovascular gene expression. Metabolic inhibitors showed a dose-dependent reduction in viability in all three groups, predominantly in PAH-EC. A different metabolic profile is present in CTEPH-EC compared to PAH-EC and suggests differences in molecular mechanisms important in the disease pathology and treatment.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 631/337 / 631/80 / 631/80/642/333 / 631/80/642/333/1465 / 692/308 / 692/4019 / 692/699 / 692/699/1785 / 692/699/75 / Adult / Aged / Cells, Cultured / Chronic Disease / Colorimetry / Endothelial cells / Endothelial Cells - metabolism / Female / Gene Expression / Glucosephosphate dehydrogenase / Glutamate Dehydrogenase - genetics / Glutamate Dehydrogenase - metabolism / Glycolysis / Glycolysis - genetics / Hexokinase - genetics / Hexokinase - metabolism / Humanities and Social Sciences / Humans / Hypertension / L-Lactate Dehydrogenase - genetics / L-Lactate Dehydrogenase - metabolism / Male / Metabolism / Middle Aged / Molecular modelling / multidisciplinary / Oxidative Phosphorylation / Patients / Phosphorylation / Pulmonary Arterial Hypertension - genetics / Pulmonary Arterial Hypertension - metabolism / Pulmonary arteries / Pulmonary artery / Pulmonary Artery - cytology / Pulmonary Embolism - genetics / Pulmonary Embolism - metabolism / Pulmonary hypertension / Pyruvate Dehydrogenase (Lipoamide) - genetics / Pyruvate Dehydrogenase (Lipoamide) - metabolism / Science / Science (multidisciplinary) / Thromboembolism / Vascular diseases / Viability