15 February 2020 by Olga Tura

Decreased glycolysis as metabolic footprint of endothelial cells in chronic thromboembolic pulmonary hypertension

Background: Chronic thromboembolic pulmonary hypertension (CTEPH) is caused by non-resolution of thrombi that obstruct main pulmonary arteries and secondary cause vascular remodeling of the pulmonary vasculature. Endothelial cells (EC) are an important component in vascular disease development. We speculated that metabolic dysregulation of EC contribute to cellular changes that promote vascular remodeling in CTEPH.

Methods: This study used endothelial cells (EC-CTEPH) isolated from specimen extracted at pulmonary endarterectomy. Proliferation and 2D-3D function assays were used to assess angiogenic potential. Expression levels of metabolic enzymes were studied at mRNA and protein level. Glucose consumption and lactate production was measured in the supernatant overlying EC-CTEPH and HPAE using BGEM cards.
Results: EC-CTEPH showed a hyperproliferative phenotype and significantly lower mRNA and protein levels of all glycolytic enzymes analyzed compared to HPAE. Transcript levels of PDK1 and GLUD1, involved in glutamine metabolism, were also downregulated. Fatty acid and pentose phosphate metabolism did not present significant differences between EC-CTEPH and HPAE. A lower glycolytic flux in EC-CTEPH was observed in terms of glucose consumption and lactate production. Functionally, EC-CTEPH have a reduced angiogenic capacity both in vitro and in vivo.

Conclusion: Our results showed that EC in human CTEPH are hyperproliferative and present a reduced angiogenesis and glycolytic metabolism compared to healthy EC. TCA and glutamine metabolism were also downregulated in EC-CTEPH. Other metabolic pathways such as FAO and PPP did not show a compensatory upregulation. More studies need to be performed to determine the role of our findings in EC-CTEPH pathogenesis.

About the author

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Olga Tura

Postdoctoral Researcher



Key Contributors

O. Tura-Ceide, Valérie F. Smolders, C. Rodríguez, I. Blanco, J. Osorio, L. Piccari, C. Bonjoch, P.H.A. Quax, M. Cascante, V. I Peinado, M. Castellà, Joan Albert Barberà Department of Pulmonary Medicine, Hospital Clínic-Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain, Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Barcelona, Diagonal 643, Barcelona, Spain, Department of Vascular Surgery, LUMC, Leiden, The Netherlands, Centro de Investigación Biomédica en Red (CIBER) de Enfermedades Respiratorias, Madrid,Spain, Department of Cardiovascular Surgery, Institut Clínic del Tòrax, Hospital Clínic, University of Barcelona, Spain.

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