Probing Shear-Induced Endothelial Activation in Vascular Conditions Using On-Chip Models.

Abstract

Hemodynamic fluctuations at vessel bifurcation impact the development of atherosclerosis and aneurysms. A novel glass capillary tube-based lithography-free technique was used for fabricating vessel bifurcations with stenosis and aneurysm at the junction of bifurcation to determine the endothelial response to arterial shear rates in vitro. At variable shear rates of 1-2000 s^-1, representative of conditions in the aorta, the endothelial cell responses under flow disturbances encountered in stenosed and aneurysmal vessels were modeled. Mechanical disturbances induce greater endothelial activation at stenosis, while increased VE-cadherin expression deters activation at dilations. The endothelial responses to disturbed flow were better observed at the area of bifurcation, where the increase in shear forces and reduced pressure marginally compensated for cellular activation. The comparative model was established using an image analysis approach for the assessment of endothelial responses toward disease progression at bifurcations. No significant differences in endothelial markers were observed under inflammatory stress and physiologically relevant mechanical stresses due to compensatory effects of inflammatory cytokines inducing NF-κβ activation, as seen using this frugal approach.