Mendoza-Zambrano Elva, Sánchez-López Verónica, Gómez-Rodríguez Belén, García-Lunar Inés, Pereda-Arnau Daniel, Jara-Palomares Luis, Elías-Hernández Teresa, García-Álvarez Ana, Otero-Candelera Remedios
Medical Surgical Unit of Respiratory Diseases, Virgen del Rocio University Hospital, 41013 Seville, Spain.
Institute of Biomedicine of Seville (IBiS) Virgen del Rocio University Hospital/CSIC/University of Seville, 41013 Seville, Spain.
Biomedicines. 2025 Jun 18;13(6):1499. doi: 10.3390/biomedicines13061499.
: 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. : 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. : 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; = 0.013). : Inflammation involving LEVs and EEVs plays a crucial role in sustaining the vascular alterations leading to pulmonary vasculature remodeling in CTEPH.
慢性血栓栓塞性肺动脉高压（CTEPH）的发病机制涉及多种因素的相互作用，包括血栓溶解不完全、内皮功能障碍和血管重塑。最近的研究强调了细胞外囊泡（EVs）在血管疾病中的作用，表明它们可能参与CTEPH的进展。本研究旨在探讨来自不同细胞来源的EVs在CTEPH发生发展中的作用。
使用11只3个月大的雄性大白猪进行了一项实验研究。对内皮来源的EVs（EEVs；CD146+）、白细胞衍生的EVs（LEVs；CD45+、CD44+）以及与间充质来源一致的EVs（CD90+、CD105+）进行了定量分析。在基线、首次栓塞后以及随后每周栓塞前进行测量。重复栓塞直至产生慢性肺动脉高压（PH）。基于这些发现，进行了一项临床病例对照研究，纳入了9例先前诊断为CTEPH的患者和18例肺栓塞患者，后者在两年随访后未发生CTEPH。
实验研究中，与间充质来源一致的EVs呈现出逐渐下降至基线水平以下的趋势；PH形成后LEVs下降，而EEVs在整个研究过程中一直升高。随后，在临床病例对照研究中，CD45+ LEVs成为CTEPH的显著相关因素，比值比（OR）为21.25（95% CI：1.91 - 236.00；P = 0.013）。
涉及LEVs和EEVs的炎症在维持导致CTEPH肺血管重塑的血管改变中起关键作用。
