Journal
SCIENTIFIC REPORTS
Volume 11, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41598-021-98320-1
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Funding
- Marie Curie Post-Doctoral Fellowship Award BIOTRACK: IDIBAPS
- Instituto de Salud Carlos III [CP17/00114]
- European Commission Horizon 2020 research and innovation program under the MOGLYNET H2020-MSCA-ITN-EJD Grant [675527]
- Spanish Society of Respiratory Medicine (SEPAR 2013)
- Catalan Society of Pneumology (SOCAP 2015)
- Fundacion Contra la Hipertension Pulmonar (FCHP)
- Institute of Health Carlos III, Spain [PI15/00582, PI18/00960]
- Fondo Europeo de Desarrollo Regional (FEDER)
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This study comprehensively analyzed the endothelial function, molecular signature, and mitochondrial profile of CTEPH-derived endothelial cells, revealing a hyperproliferative phenotype with increased expression of adhesion molecules, decreased apoptosis, eNOS activity, and migration capacity compared to healthy endothelial cells. Furthermore, CTEPH-EC exhibited altered mitochondrial dynamics, increased mitochondrial respiration, and an unbalanced production of reactive oxygen species and antioxidants. Modulation of redox, mitochondrial homeostasis, and adhesion molecule overexpression could be potential novel targets and biomarkers in treating CTEPH.
Pulmonary endarterectomy (PEA) resected material offers a unique opportunity to develop an in vitro endothelial cell model of chronic thromboembolic pulmonary hypertension (CTEPH). We aimed to comprehensively analyze the endothelial function, molecular signature, and mitochondrial profile of CTEPH-derived endothelial cells to better understand the pathophysiological mechanisms of endothelial dysfunction behind CTEPH, and to identify potential novel targets for the prevention and treatment of the disease. Isolated cells from specimens obtained at PEA (CTEPH-EC), were characterized based on morphology, phenotype, and functional analyses (in vitro and in vivo tubule formation, proliferation, apoptosis, and migration). Mitochondrial content, morphology, and dynamics, as well as high-resolution respirometry and oxidative stress, were also studied. CTEPH-EC displayed a hyperproliferative phenotype with an increase expression of adhesion molecules and a decreased apoptosis, eNOS activity, migration capacity and reduced angiogenic capacity in vitro and in vivo compared to healthy endothelial cells. CTEPH-EC presented altered mitochondrial dynamics, increased mitochondrial respiration and an unbalanced production of reactive oxygen species and antioxidants. Our study is the foremost comprehensive investigation of CTEPH-EC. Modulation of redox, mitochondrial homeostasis and adhesion molecule overexpression arise as novel targets and biomarkers in CTEPH.
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