Role of Extracellular Vesicles in Chronic Post-Embolic Pulmonary Hypertension: Data from an Experimental Animal Model and Patients
<b>Background</b>: The pathogenesis of chronic thromboembolic pulmonary hypertension (CTEPH) involves a multifaceted interplay of factors, including incomplete thrombus resolution, endothelial dysfunction, and vascular remodeling. Recent studies have highlighted the role of extracellular...
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MDPI AG
2025-06-01
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| author | Elva Mendoza-Zambrano Verónica Sánchez-López Belén Gómez-Rodríguez Inés García-Lunar Daniel Pereda-Arnau Luis Jara-Palomares Teresa Elías-Hernández Ana García-Álvarez Remedios Otero-Candelera |
| author_facet | Elva Mendoza-Zambrano Verónica Sánchez-López Belén Gómez-Rodríguez Inés García-Lunar Daniel Pereda-Arnau Luis Jara-Palomares Teresa Elías-Hernández Ana García-Álvarez Remedios Otero-Candelera |
| author_sort | Elva Mendoza-Zambrano |
| collection | DOAJ |
| description | <b>Background</b>: The pathogenesis of chronic thromboembolic pulmonary hypertension (CTEPH) involves a multifaceted interplay of factors, including incomplete thrombus resolution, endothelial dysfunction, and vascular remodeling. Recent studies have highlighted the role of extracellular vesicles (EVs) in vascular diseases, suggesting their potential involvement in CTEPH progression. This study aims to investigate the role of EVs from various cellular sources in the development of CTEPH. <b>Methods</b>: An experimental study was conducted using 11 male three-month-old Large-White pigs. The EVs of endothelial origin (EEVs; CD146+), leukocyte-derived EVs (LEVs; CD45+, CD44+), and consistent with mesenchymal-origin EVs (CD90+, CD105+) were quantified. Measurements were taken at baseline, after the first embolization, and prior to each subsequent weekly embolization. Embolizations were repeated until chronic pulmonary hypertension (PH) was generated. Based on these findings, a clinical case-control study was performed involving nine patients previously diagnosed with CTEPH and 18 patients with pulmonary embolism who did not develop CTEPH after two years of follow-up. <b>Results</b>: The experimental study, consistent with the mesenchymal-origin EVs, exhibited a progressive decrease below baseline levels; LEVs decreased after PH was established, while EEVs remained elevated throughout the study. Subsequently, in the clinical case-control study, CD45+ LEVs emerged as a significant association of CTEPH, with an odds ratio (OR) of 21.25 (95% CI: 1.91–236.00; <i>p</i> = 0.013). <b>Conclusions</b>: Inflammation involving LEVs and EEVs plays a crucial role in sustaining the vascular alterations leading to pulmonary vasculature remodeling in CTEPH. |
| format | Article |
| id | doaj-art-0b9dc4d4db2e4aaf97dc0bf2d03b233f |
| institution | Kabale University |
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| language | English |
| publishDate | 2025-06-01 |
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| spelling | doaj-art-0b9dc4d4db2e4aaf97dc0bf2d03b233f2025-08-20T03:26:20ZengMDPI AGBiomedicines2227-90592025-06-01136149910.3390/biomedicines13061499Role of Extracellular Vesicles in Chronic Post-Embolic Pulmonary Hypertension: Data from an Experimental Animal Model and PatientsElva Mendoza-Zambrano0Verónica Sánchez-López1Belén Gómez-Rodríguez2Inés García-Lunar3Daniel Pereda-Arnau4Luis Jara-Palomares5Teresa Elías-Hernández6Ana García-Álvarez7Remedios Otero-Candelera8Medical Surgical Unit of Respiratory Diseases, Virgen del Rocio University Hospital, 41013 Seville, SpainInstitute of Biomedicine of Seville (IBiS) Virgen del Rocio University Hospital/CSIC/University of Seville, 41013 Seville, SpainMedical Surgical Unit of Respiratory Diseases, Virgen del Rocio University Hospital, 41013 Seville, SpainNational Center of Cardiovascular Research (CNIC), Cardiology Department, La Moraleja University Hospital, 28050 Madrid, SpainBiomedical Research Center for Cardiovascular Diseases (CIBERCV), 28029 Madrid, SpainMedical Surgical Unit of Respiratory Diseases, Virgen del Rocio University Hospital, 41013 Seville, SpainMedical Surgical Unit of Respiratory Diseases, Virgen del Rocio University Hospital, 41013 Seville, SpainBiomedical Research Center for Cardiovascular Diseases (CIBERCV), 28029 Madrid, SpainMedical Surgical Unit of Respiratory Diseases, Virgen del Rocio University Hospital, 41013 Seville, Spain<b>Background</b>: The pathogenesis of chronic thromboembolic pulmonary hypertension (CTEPH) involves a multifaceted interplay of factors, including incomplete thrombus resolution, endothelial dysfunction, and vascular remodeling. Recent studies have highlighted the role of extracellular vesicles (EVs) in vascular diseases, suggesting their potential involvement in CTEPH progression. This study aims to investigate the role of EVs from various cellular sources in the development of CTEPH. <b>Methods</b>: An experimental study was conducted using 11 male three-month-old Large-White pigs. The EVs of endothelial origin (EEVs; CD146+), leukocyte-derived EVs (LEVs; CD45+, CD44+), and consistent with mesenchymal-origin EVs (CD90+, CD105+) were quantified. Measurements were taken at baseline, after the first embolization, and prior to each subsequent weekly embolization. Embolizations were repeated until chronic pulmonary hypertension (PH) was generated. Based on these findings, a clinical case-control study was performed involving nine patients previously diagnosed with CTEPH and 18 patients with pulmonary embolism who did not develop CTEPH after two years of follow-up. <b>Results</b>: The experimental study, consistent with the mesenchymal-origin EVs, exhibited a progressive decrease below baseline levels; LEVs decreased after PH was established, while EEVs remained elevated throughout the study. Subsequently, in the clinical case-control study, CD45+ LEVs emerged as a significant association of CTEPH, with an odds ratio (OR) of 21.25 (95% CI: 1.91–236.00; <i>p</i> = 0.013). <b>Conclusions</b>: Inflammation involving LEVs and EEVs plays a crucial role in sustaining the vascular alterations leading to pulmonary vasculature remodeling in CTEPH.https://www.mdpi.com/2227-9059/13/6/1499pulmonary embolismchronic thromboembolic pulmonary hypertensionextracellular vesiclesendothelial dysfunctionvascular remodeling |
| spellingShingle | Elva Mendoza-Zambrano Verónica Sánchez-López Belén Gómez-Rodríguez Inés García-Lunar Daniel Pereda-Arnau Luis Jara-Palomares Teresa Elías-Hernández Ana García-Álvarez Remedios Otero-Candelera Role of Extracellular Vesicles in Chronic Post-Embolic Pulmonary Hypertension: Data from an Experimental Animal Model and Patients Biomedicines pulmonary embolism chronic thromboembolic pulmonary hypertension extracellular vesicles endothelial dysfunction vascular remodeling |
| title | Role of Extracellular Vesicles in Chronic Post-Embolic Pulmonary Hypertension: Data from an Experimental Animal Model and Patients |
| title_full | Role of Extracellular Vesicles in Chronic Post-Embolic Pulmonary Hypertension: Data from an Experimental Animal Model and Patients |
| title_fullStr | Role of Extracellular Vesicles in Chronic Post-Embolic Pulmonary Hypertension: Data from an Experimental Animal Model and Patients |
| title_full_unstemmed | Role of Extracellular Vesicles in Chronic Post-Embolic Pulmonary Hypertension: Data from an Experimental Animal Model and Patients |
| title_short | Role of Extracellular Vesicles in Chronic Post-Embolic Pulmonary Hypertension: Data from an Experimental Animal Model and Patients |
| title_sort | role of extracellular vesicles in chronic post embolic pulmonary hypertension data from an experimental animal model and patients |
| topic | pulmonary embolism chronic thromboembolic pulmonary hypertension extracellular vesicles endothelial dysfunction vascular remodeling |
| url | https://www.mdpi.com/2227-9059/13/6/1499 |
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