Design of a Cone and Plate Co-culture Device to Investigate the Effects of Fluid Shear Stress
Thursday, June 2, 2016
3:00 PM-5:00 PM
BIOMED Master's Thesis Defense
Title:
Design of a Cone and Plate Co-culture Device To Investigate the Effects of Fluid Shear Stress and Free Fatty Acids on Endothelial Nitric Oxide Production
Speaker:
Nicholas Houriet, Master's Candidate, School of Biomedical Engineering, Science and Health Systems
Advisors:
Alisa Morss Clyne, PhD, Associate Professor, Department of Mechanical Engineering and Mechanics
Ken Barbee, PhD, Professor and Interim Director, School of Biomedical Engineering, Science and Health Systems
Abstract:
Metabolic syndrome and obesity in particular are significant cardiovascular disease risk factors. Excessive central adipose (fat) tissue is strongly linked to insulin resistance, which may contribute to systemic and adipose tissue vascular inflammation. Insulin resistant and obese individuals have increased levels of circulating free fatty acids, which inhibit insulin-induced production of atheroprotective nitric oxide by endothelial cells in vitro. Decreased endothelial nitric oxide can further lead to chronic inflammation of the vasculature and adipose tissue. Furthermore, insulin resistant and obese individuals display reduced adipose tissue blood flow. Thus the FFA-induced reduction in endothelial nitric oxide production may further decrease shear stress-induced endothelial nitric oxide production and exacerbate adipose tissue inflammation and metabolic disease. The objective of this thesis is to elucidate the effects of FFAs on endothelial cell response to fluid shear stress. I hypothesize that shear stress leads to endothelial nitric oxide synthase phosphorylation in the presence of FFAs. If proved true, this would suggest that restoring adipose tissue blood flow may abrogate adipose tissue inflammation and metabolic syndrome.
Since existing in vitro fluid shear stress testing devices cannot test the effects of shear stress on endothelial cells in a 3D co-culture system with adipocytes, this thesis first presents a new cone and plate flow device with a 3D hydrogel co-culture component. The cone and plate flow system successfully created laminar fluid shear stress in both acute (5 minute) and chronic (24 hour) bovine aortic endothelial cells, demonstrated by increased endothelial nitric oxide synthase phosphorylation and cell alignment, respectively. Finally, FFAs were demonstrated to inhibit insulin-induced endothelial nitric oxide synthase phosphorylation in static culture; however effect of FFAs on flow-induced nitric oxide production have yet to be examined. The results presented here support further examination of the role of shear stress and FFAs in vascular disease.
Contact Information
Ken Barbee
215-895-1335
barbee@drexel.edu