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Probing Shear-Induced Endothelial Activation in Vascular Conditions Using On-Chip Models
Swachhatoa Ghosh1, Shreya Mandal2, Abhijit Das2
1School of Medical Science and Technology, IIT Kharagpur, Kharagpur 721302, India.
ACS Biomaterials Science & Engineering
|April 11, 2025
Summary
This study models endothelial cell responses to arterial shear rates in vitro using a novel technique. Mechanical disturbances at vessel bifurcations activate endothelial cells, with differing responses in stenosed versus dilated areas.
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.
