Ph.D Thesis


Ph.D StudentOrit Braun Benyamin
SubjectInitiation of Atherosclerosis - Correlating near Wall
Flow Patterns with Endothelial Activation Markers
DepartmentDepartment of Aerospace Engineering
Supervisors Full Professors Cohen Jacob
Ms. Resnick Nitzan
Full Thesis textFull thesis text - English Version


Abstract

Atheosclerosis, a chronic cardiovascular disease and its complications are a major morbidity cause in the western world. The focal distribution of atherosclerotic lesions in areas of aortic branches and bifurcations, suggests that hemodynamic forces and more specifically flow shear stress play a major role in atherogenesis initiation. Studies with cultured cells suggested that shear stress patterns in the bifurcation region are not homogeneous, pointing at “micro environment” of shear stress that coincide with morphological variations and growth patterns of the endothelium. However, these microenvironments are not well characterized by either their fluid dynamics or by the response of the endothelium.

This research is unique in that it attempts to critically test and control the fluid regimes involved in the shear stresses and to establish a link between the endothelial cellular response and the local flow patterns to which the cells are exposed to. 

Two similar experimental systems were constructed with identical geometry (a symmetric constriction) and flow conditions - one for the biological experiments and the other for flow measurements in a PIV (Particle Image Velocimetry) system with special adaptations and modifications in order to allow near wall measurement The flow field was measured in a 3D model of a straight and constricted capillary at different Reynolds numbers, with a near wall resolution of 60┬Ám and the wall shear was calculated. In the biological experimental system, confluent monolayer of bovine aortic endothelial cells (BAEC) was grown inside 2.5mm capillaries.  The cells were subjected for 24-48 hours to the flow and then fixed and stained for several biological markers.

A correlation was found between the activation of NFκB to regions of flow separation and reversal flow. In a straight capillary subjected to laminar flow (Reynolds = 180) the activation of NFκB was prominently lower that the activation level just up stream and down stream to the capillary constricted area. Staining results for β catenin in regions exposed to laminar was continuous and distributed around the entire periphery of cells. In the reattachment region which had been exposed to 24hours of disturbed flow, however, the β catenin staining became intermittent, showing frequent gaps.

Our results prove that a combined experimental system, which allows flow measurement on one hand and biological response on the other, is a powerful tool for the investigation of the crucial events associated with the early stages of Athersclerosis by correlating the exact blood flow pattern to the biological events.