Verhaegen Janne, Willems Lynn, Wagenaar Allard, Spreuwers Ruben, Dahdah Nessrine, Aversa Lucia, Verbelen Tom, Delcroix Marion, Quarck Rozenn
Laboratory of Respiratory Diseases & Thoracic Surgery (BREATHE), Department of Chronic Diseases & Metabolism (CHROMETA) KU Leuven - University of Leuven Leuven Belgium.
Department of Cardiac Surgery University Hospitals Leuven Leuven Belgium.
Pulm Circ. 2025 May 12;15(2):e70096. doi: 10.1002/pul2.70096. eCollection 2025 Apr.
Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare complication of pulmonary embolism, characterized by the presence of organized fibro-thrombotic material that partially or fully obstructs the lumen of large pulmonary arteries, microvasculopathy, and enlargement of the bronchial systemic vessels. The precise mechanisms underlying CTEPH remain unclear. However, defective angiogenesis and altered pulmonary arterial endothelial cell (PAEC) function may contribute to disease progression. Despite the observation of differences in histological features, shear stress and ischemia along the pulmonary vascular tree, the potential contribution of PAEC phenotype and function to these disparate aspects remains unexplored. Based on these observations, we postulated that angiogenic capacities and endothelial barrier function may contribute to disparities in histological features observed along the pulmonary vascular tree. We thus explored the histological characteristics of the pulmonary vascular tree using pulmonary arterial lesions obtained during pulmonary endarterectomy (PEA). We focused on the angiogenic vascular endothelial growth factor (VEGF)-A/VEGF receptor-2 (VEGFR2) axis and collagen 15A1 (COL15A1), a potential marker of endothelial cells of the systemic circulation. Concurrently, we examined In Vitro angiogenic properties and barrier function of PAECs derived from large and (sub)-segmental pulmonary arterial lesions. (Sub)-segmental pulmonary arterial lesions were abundantly recanalized by neovessels, paralleled by an enriched expression of VEGFR2. VEGF-A expression was more pronounced in large pulmonary arterial lesions. Nevertheless, no significant difference was discerned in In Vitro angiogenic capacities and barrier integrity of PAECs isolated from large and (sub)-segmental pulmonary arterial lesions. Importantly, our findings revealed the presence of endothelial cells (CD31) expressing COL15A1, as well as CD31 cells that did not express COL15A1. This suggests that endothelial cells from both systemic and pulmonary circulation contribute to lesion recanalization. Despite disparate in situ angiogenic cues in VEGF-A/VEGFR2 axis between large and (sub)-segmental pulmonary arterial lesions in CTEPH, In Vitro angiogenic capacities and barrier function remain unaltered.
慢性血栓栓塞性肺动脉高压（CTEPH）是肺栓塞的一种罕见并发症，其特征是存在有组织的纤维血栓物质，该物质部分或完全阻塞大肺动脉管腔、微血管病变以及支气管体循环血管扩张。CTEPH的确切发病机制尚不清楚。然而，血管生成缺陷和肺动脉内皮细胞（PAEC）功能改变可能导致疾病进展。尽管观察到肺血管树的组织学特征、剪切应力和缺血存在差异，但PAEC表型和功能对这些不同方面的潜在贡献仍未得到探索。基于这些观察结果，我们推测血管生成能力和内皮屏障功能可能导致肺血管树中观察到的组织学特征差异。因此，我们使用肺动脉内膜剥脱术（PEA）期间获得的肺动脉病变来探索肺血管树的组织学特征。我们重点研究了血管生成血管内皮生长因子（VEGF）-A/VEGF受体-2（VEGFR2）轴和胶原蛋白15A1（COL15A1），后者是体循环内皮细胞的潜在标志物。同时，我们检测了源自大的和（亚）段肺动脉病变的PAEC的体外血管生成特性和屏障功能。（亚）段肺动脉病变被新生血管大量再通，同时伴有VEGFR2表达增加。VEGF-A在大的肺动脉病变中表达更明显。然而，从大的和（亚）段肺动脉病变中分离出的PAEC的体外血管生成能力和屏障完整性没有明显差异。重要的是，我们的研究结果显示存在表达COL15A1的内皮细胞（CD31）以及不表达COL15A1的CD31细胞。这表明来自体循环和肺循环的内皮细胞都参与了病变再通。尽管CTEPH中大的和（亚）段肺动脉病变在VEGF-A/VEGFR2轴上的原位血管生成信号不同，但体外血管生成能力和屏障功能仍未改变。
