Effects of Simultaneous Wall Shear Stress and Circumferential Strain on Endothelial Cell Junctions
Open Access
- Author:
- Berardi, Danielle Elizabeth
- Graduate Program:
- Bioengineering
- Degree:
- Doctor of Philosophy
- Document Type:
- Dissertation
- Date of Defense:
- March 20, 2009
- Committee Members:
- John Michael Tarbell, Dissertation Advisor/Co-Advisor
Peter J Butler, Committee Chair/Co-Chair
Peter J Butler / John M Tarbell, Committee Chair/Co-Chair
Herbert Herling Lipowsky, Committee Member
David A Antonetti, Committee Member
Cheng Dong, Committee Member - Keywords:
- junctions
endothelial cells
circumferential strain
wall shear stress
stress phase angle - Abstract:
- <P ALIGN="JUSTIFY">Complex hemodynamics play a role in the localization and development of atherosclerosis. Endothelial cells (ECs) lining blood vessel walls are directly influenced by various hemodynamic forces: simultaneous wall shear stress (WSS), normal stress, and circumferential strain (CS) due to pulsatile flow, pressure, and diameter changes. As such, ECs may sense and transduce these forces into biomolecular responses at intercellular junctions. A hemodynamic simulator is used to investigate the combined effects of WSS and CS on EC junctions with emphasis on the stress phase angle (SPA), the temporal phase difference between WSS and CS. Regions of the circulation with highly negative SPA, such as the coronary arteries and carotid bifurcation, are more susceptible to the development of atherosclerosis.</P> <P ALIGN="JUSTIFY">At 5 hours, zonula occludens-1 relative protein expression was significantly higher for the atheroprotective SPA = 0<SUP>o</SUP> compared to the atherogenic SPA = -180<SUP>o</SUP> while apoptosis was significantly higher for SPA = -180<SUP>o</SUP> than SPA = 0<SUP>o</SUP>. This decrease in tight junction protein and increase in cell turnover, and thus leaky junction presence, may indicate a decreased junctional stability and a higher paracellular permeability for the atherogenic SPA = -180<SUP>o</SUP> than for SPA = 0<SUP>o</SUP>. Meanwhile, at 12 hours, protein expression levels and mitosis were not significantly different between SPA = -180<SUP>o</SUP> and SPA = 0<SUP>o</SUP>. Finally, changes in cell elongation and alignment were negligible at these time points.</P> <P ALIGN="JUSTIFY">Additionally, using a parallel plate flow chamber, the effects of short- and long-term exposure of ECs to WSS were examined for junctional markers as ECs remodel and align in the direction of flow over time. Indeed, ECs exposed to WSS for 24 hours significantly increased the alignment and elongation while significantly decreasing mitosis.</P>