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

Area of Science:

• Biomedical Engineering
• Cardiovascular Research
• Cell Biology

Background:

• Hemodynamic fluctuations at vessel bifurcations are implicated in atherosclerosis and aneurysm development.
• Understanding endothelial cell response to arterial shear stress is crucial for cardiovascular disease research.

Purpose of the Study:

• To fabricate in vitro models of vessel bifurcations with stenosis and aneurysm.
• To investigate endothelial cell responses to varying arterial shear rates and flow disturbances.
• To establish a comparative model for assessing endothelial responses in disease progression.

Main Methods:

• A novel, lithography-free glass capillary tube technique was employed for fabricating vessel bifurcations.
• Endothelial cell responses were modeled at shear rates ranging from 1-2000 s^-1, simulating aortic conditions.
• Image analysis was utilized for assessing endothelial activation and marker expression (e.g., VE-cadherin, NF-κβ).

Main Results:

• Mechanical disturbances induced greater endothelial activation at stenosed regions.
• Increased VE-cadherin expression was observed to deter endothelial activation in dilated (aneurysmal) areas.
• Compensatory effects between inflammatory cytokines and mechanical stresses were noted, with no significant difference in endothelial markers under combined stress.

Conclusions:

• The study successfully modeled endothelial responses to disturbed flow at vessel bifurcations using a frugal, in vitro approach.
• Differential endothelial activation at stenosis versus dilation highlights the complex mechanobiology of cardiovascular diseases.
• The findings provide insights into endothelial cell behavior under various hemodynamic conditions relevant to atherosclerosis and aneurysm development.