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Title: Effects of multidirectional flow on cultured endothelium
Author: Ghim, Mean Chung
ISNI:       0000 0004 6061 7141
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2017
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Endothelial permeability to circulating macromolecules and patterns of haemodynamic wall shear stress both vary from site to site within the arterial system. Influences of local blood flow on macromolecule transport across the endothelium may account for the patchy nature of atherosclerosis, but the routes for such transport and their modification by flow are highly controversial. The current consensus attributes the site specific formation of atherosclerotic lesions within the vasculature to low and oscillatory hemodynamic wall shear stress. However, effects of multidirectional shear stress, which occur in lesion prone regions, are not fully understood. An orbital shaker was utilised to impose chronic multidirectional shear stresses on cultured porcine aortic endothelial cells grown in multi-well plates. The orbital motion induced a wave of culture medium which rotated around the well. The shear stresses experienced by the endothelial cells at each location on the bottom of the well and at each time during the orbit were obtained using numerical methods. Spatially-resolved measurements of permeability were made by using molecular recognition between the substrate underneath the cells and different sized tracers initially placed above them. The tracer bound to the substrate once it was transported through the monolayer, and was detected by confocal microscopy. Numerical methods revealed cells at the centre of the well experienced multidirectional shear stress whereas cells at the edge were subjected to uniaxial shear stress. The transport routes of macromolecules through the monolayer were dependent on size of the macromolecules and their modification by different shear stress characteristics also varied. Chronic multidirectional shear stress appears to be proatherogenic, priming endothelial cell for inflammation and affecting the barrier function of the monolayer. Combining spatially-resolved measurements of permeability with the orbital shaker model to study the effects of chronic multidirectional flow will be a useful model for further in vitro studies.
Supervisor: Weinberg, Peter Sponsor: Imperial College London
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral