Impact of Spatial and Temporal Stability of Aneurismal Flow Vortices on
Vascular Endothelial Cells
Abstract
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/cm2 wall shear stress) or low (<1
dynes/cm2) 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.