Effects of Neighboring Regions of Disturbed Flow on the Functional Phenotype of Endothelial Cells
Tuesday, February 27, 2018
3:00 PM-5:00 PM
BIOMED PhD Research Proposal
The Effects of Neighboring Regions of Disturbed Flow on the Functional Phenotype of Endothelial Cells Subjected to Laminar and Flow
Jason Sedlak, PhD Candidate, School of Biomedical Engineering, Science and Health Systems, Drexel University
Alisa Morss Clyne, PhD, Associate Professor, Department of Mechanical Engineering and Mechanics, Drexel Univeristy
Kenneth A. Barbee, PhD, Professor, Senior Associate Dean and Associate Dean for Research, School of Biomedical Engineering, Science and Health Systems, Drexel University
Cardiovascular disease (CVD) is the leading cause of death in both men and women. There is a strong correlation between the vascular location where CVD develops and the blood hemodynamics at that location. Laminar blood flow, which is associated with high shear stress, is disrupted by complex arterial geometry, forming recirculating eddies (disturbed flow) and low shear stress, which induce endothelial dysfunction. Previous research has identified many mechanisms through which disturbed flow generates the vulnerable endothelial phenotype, but that work only examines cells exposed to disturbed or laminar flow. In vivo, endothelial cells are subjected to a continuum of disturbed and laminar flow, side by side.
This research uses an in vitro disturbed flow model to elucidate how neighboring cells adapted to laminar and disturbed flow alter each other’s respective phenotype. It is hypothesized that the disturbed flow-conditioned cells reduce the protective phenotype of laminar flow-conditioned cells in their proximity. Endothelial cells will be conditioned in laminar (20 dynes/cm2) or laminar/disturbed-mixed flow conditions and evaluated for functional phenotype, including cytoskeleton organization, permeability, and capacity to recruit leukocytes. Results from this study can ultimately lead to more effective and targeted methods to diagnose and treat cardiovascular diseases.