3D modelling of pulmonary arterial stenosis and endothelial dysfunction in CTEPH
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Published version
Supplementary information
Author(s)
Type
Journal Article
Abstract
Chronic thromboembolic pulmonary hypertension (CTEPH) arises from progressive thrombotic occlusion of pulmonary arteries, involving vessel blockage by unresolved thrombi and small vessel arteriopathy. This disrupts blood flow, increases lung pressure, and alters vessel geometry, contributing to endothelial dysfunction. However, the mechanisms remain unclear. To study these interactions, we developed microfluidic 3D models of pulmonary arteries with 30–80% stenosis using CTPAs from CTEPH and acute pulmonary embolism (APE) patients, in silico flow simulations, 3D printing, and soft lithography. Unlike standard circular channels, we designed semi-circular channels enclosed by a coverslip, which computational modelling confirmed closely mimics real vessel flow dynamics. Human pulmonary artery endothelial cells (HPAECs) cultured in 30–80% stenosis channels exhibited increased expression of pro-inflammatory, pro-thrombotic, and pro-angiogenic genes, with responses varying by stenosis severity and location. Cells in post-stenotic dilatation regions (60–80% stenosis) lost alignment and junctional integrity due to disturbed flow. The transcriptional profile of HPAECs from 80% stenosis channels closely resembled that of CTEPH pulmonary endarterectomy specimens. Platelet adhesion, dependent on von Willebrand factor (VWF), varied with stenosis severity and flow rate. Low perfusion rates increased adhesion in stenotic regions, while higher flow rates promoted adhesion post-stenosis. Our patient data-based stenosis models provide a robust platform for studying the effects of vascular geometry on blood flow, endothelial responses, and platelet aggregation, advancing research on CTEPH, pulmonary embolism, and other diseases associated with vascular occlusion.
Date Issued
2025-09-07
Date Acceptance
2025-07-08
Citation
Lab on a Chip: miniaturisation for chemistry, physics, biology, materials science and bioengineering, 2025, 25 (17), pp.4369-4384
ISSN
1473-0189
Publisher
Royal Society of Chemistry
Start Page
4369
End Page
4384
Journal / Book Title
Lab on a Chip: miniaturisation for chemistry, physics, biology, materials science and bioengineering
Volume
25
Issue
17
Copyright Statement
© The Royal Society of Chemistry 2025. This article is licensed under aCreative Commons Attribution-NonCommercial 3.0 Unported Licence (https://creativecommons.org/licenses/by-nc/3.0/)
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Publication Status
Published
Date Publish Online
2025-07-16