Impact of Spatial and Temporal Stability of Aneurismal Flow Vortices on Vascular Endothelial Cells

Disturbed flow vortices are linked with altered vascular endothelial cell (EC) morphology and protein expression indicative of intracranial aneurysms (IA). Unfortunately, lesser known is the impact of vortex spatial and temporal stability on EC changes. In this study, the interplay between vortex stability and EC changes was investigated by a novel combination of parallel plate flow chamber (PPFC) design and computational analysis. ECs were exposed to laminar (7.5 dynes/cm 2 wall shear stress) or low (<1 dynes/cm 2 ) stress vortical flow using PPFCs. Immunofluorescent imaging analyzed EC morphology, while ELISA tests quantified VE-cadherin (cell-cell adhesion), VCAM-1 (macrophage-EC adhesion), and cleaved caspase-3 (apoptotic signal) expression. PPFC flow was simulated, then vortex stability calculated via the temporally averaged degree of (volume) overlap (TA-DVO) of vortices within a given area. EC morphological changes were independent of vortex stability. Increased stability promoted VE-cadherin degradation (correlation coefficient r = -0.84) and 5-fold increased cleaved caspase-3 post 24-hrs in stable (TA-DVO 0.736+0.05) vs unstable (TA-DVO 0.606+0.2) vortices. ECs in stable vortices displayed a 4.5-fold increase in VCAM-1 than unstable counterparts after 12-hrs flow. Flow vortices of greater spatial and temporal stability impart greater degrees of EC changes related to inflammation, cell-cell adhesion, and apoptosis, than unstable vortices.