期刊
SCIENTIFIC REPORTS
卷 12, 期 1, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s41598-022-06238-z
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资金
- Miguel Servet grant from the Instituto de Salud Carlos III [CP17/00114]
- European Commission [675527]
- Spanish Society of Respiratory Medicine (SEPAR)
- Catalan Society of Pneumology (SOCAP)
- Fundacion Contra la Hipertension Pulmonar (FCHP)
- Institute of Health Carlos III, Spain [PI18/00960]
- Fondo Europeo de Desarrollo Regional (FEDER)
- Dutch Cardiovas-cular Research Alliance: the Dutch Heart Foundation
- Dutch Federation of University Medical Centers
- Netherlands Organization for Health Research and Development
- Royal Netherlands Academy of Sciences [2012-2008, 2018-2023]
This study compares the metabolic characteristics of endothelial cells from patients with chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary arterial hypertension (PAH), and finds differences between them, suggesting different disease pathology and treatment mechanisms.
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.
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