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These geometric irregularities produce spatial heterogeneity in wall shear stress (WSS), which plays a critical role in endothelial dysfunction and early immune cell recruitment during atherogenesis. However, the dynamic effect of spatial heterogeneity of wall shear stress on endothelial\u2010immune interactions remains unclear. A multiscale computational model that integrates hemodynamics, endothelial cell phenotype transitions, and immune responses was developed. The model is used to investigate endothelial cell (EC) phenotype transitions and immune cell dynamics under varying damage threshold (\n                    <jats:italic>D<\/jats:italic>\n                    <jats:sub>NO<\/jats:sub>\n                    ) conditions. Low\u2010shear stress regions were found to expand with increasing\n                    <jats:italic>D<\/jats:italic>\n                    <jats:sub>NO<\/jats:sub>\n                    . Nitric oxide (NO) production was decreased, leading to accelerated EC activation and death. Monocyte Chemoattractant Protein\u20101 (MCP\u20101) expression was elevated, and monocyte recruitment and differentiation were enhanced, resulting in a higher proportion of pro\u2010inflammatory M1 macrophages. The model reproduced experimental observations and provided robust predictions under different\n                    <jats:italic>D<\/jats:italic>\n                    <jats:sub>NO<\/jats:sub>\n                    scenarios. These results indicate that dynamic WSS drives EC state transitions and regulates immune cell recruitment and differentiation, providing a framework for studying vascular inflammation. Spatially heterogeneous WSS induces local NO depletion, which accelerates EC activation and death in low\u2010shear stress regions, explaining focal endothelial dysfunction. EC injury further increases MCP\u20101 production, enhances monocyte recruitment, and promotes macrophage polarization toward a pro\u2010inflammatory phenotype, demonstrating the ability of the model to capture flow\u2010dependent vascular immune dynamics and inflammatory lesion development. This work provides mechanistic insight into the interplay between mechanical forces and vascular immune responses and may guide strategies for preventing endothelial injury and promoting anti\u2010inflammatory therapy.\n                  <\/jats:p>","DOI":"10.1002\/cnm.70137","type":"journal-article","created":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T04:41:21Z","timestamp":1768192881000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A Multiscale Computational Model of Endothelial\u2010Immune Cell Interactions Regulated by Dynamic Wall Shear Stress"],"prefix":"10.1002","volume":"42","author":[{"given":"Yu\u2010Yuan","family":"Zhang","sequence":"first","affiliation":[{"name":"Institute of Cardio\u2010Cerebrovascular Medicine, Central Hospital of Dalian University of Technology  Dalian Liaoning People's Republic of China"},{"name":"School of Biomedical Engineering, Faculty of Medicine, Dalian University 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