Objective Computational fluid dynamics (CFD) has implicated aberrant flow stress in the pathophysiology of intracranial aneurysms. However, the direct causation of endothelial inflammatory response by aberrant flow stress in human aneurysm pathology remains unclear. This study aims to study the biological response to aberrant flow stress within intracranial aneurysms using precision three-dimensional (3D) cerebrovascular models.
Methods Eight intracranial aneurysm models were created using 3D printing technology. Human umbilical vein endothelial cells (HUVECs) were attached to the aneurysm model surfaces, and flow stress, calculated from CFD studies, was applied. Following flow circulation, RNA was extracted from endothelial cells. The Nanostring nCounter Assay and quantitative real-time polymerase chain reaction (qPCR) were employed to evaluate endothelial responses to flow stress in the aneurysms.
Results CFD studies demonstrated laminar flow in parent arteries and abnormal flow characteristics in intracranial aneurysms, including low wall shear stress, impinging flow, and vortex. The Nanostring nCounter Assay revealed up-regulation of inflammatory genes (e.g., TNF-a) and down-regulation of anti-inflammatory genes (e.g., KLF2) in aneurysms compared to the parent arteries. Notably, Monocyte Chemoattractant Protein-1 (MCP-1) was specifically up-regulated in sidewall compared to bifurcation aneurysms. The qPCR analyses showed that Increased MCP-1 expression was observed in aneurysms with vortex flow, regardless of wall shear stress status or sidewall vs. bifurcation.
Conclusions Vortex flow in intracranial aneurysm geometry can induce MCP-1 expression in endothelial cells, potentially accounting for macrophage infiltration in some aneurysms. This innovative approach, using patient-specific geometry, provides valuable insights into endothelial biology under complex flow conditions in intracranial aneurysms.
Disclosures N. Kaneko: 1; C; NIH, Brain Aneurysm Foundation, Joe Niekro Foundation Research Grant/SNIS Foundation, Tarsadia Foundation, Jennifer Carroll Wilson Aneurysm Research Fund, Frederick Gardner Cottrell Foundation. O. Selim: None. J. Cebral: 1; C; NIH. Y. Komuro: None. S. Tateshima: 1; C; Joe Niekro Foundation Research Grant/SNIS Foundation. L. Guo: None. J. Villablanca: None. Y. Tobe: 1; C; NIH. A. Robertson: 1; C; NIH. G. Duckwiler: 1; C; Tarsadia Foundation, Jennifer Carroll Wilson Aneurysm Research Fund, Frederick Gardner Cottrell Foundation. J. Hinman: 1; C; Brain Aneurysm Foundation.
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