A Modified Parallel Plate Flow Chamber to Study Local Endothelial Response to Recirculating Disturbed Flow

Area of Science:

• Cardiovascular Biology
• Biomedical Engineering
• Hemodynamics

Background:

• Atherosclerosis commonly occurs at arterial sites with low shear stress and disturbed blood flow.
• Endothelial cells (ECs) dysfunction is a critical early event in atheroma development.
• Understanding the role of hemodynamics in EC dysfunction is crucial for preventing atherosclerosis.

Purpose of the Study:

• To investigate the impact of disturbed blood flow on endothelial cell function using a modified in vitro flow chamber.
• To analyze how altered shear stress affects EC morphology, nitric oxide production, proliferation, permeability, and monocyte adhesion.
• To elucidate the complex relationship between hemodynamics and endothelial dysfunction in the context of atherosclerosis.

Main Methods:

• Modification of a parallel plate flow chamber with baffles to create recirculating disturbed flow regions.
• Computational fluid dynamics (CFD) to predict shear stress distribution, identifying areas below the atheroprotective threshold.
• Exposure of bovine aortic endothelial cells (BAECs) to laminar and disturbed flow conditions for 36 hours.
• Assessment of EC morphology, nitric oxide (NO) production, proliferation, permeability, and monocyte adhesion using microscopy techniques.

Main Results:

• ECs exposed to laminar flow (20 dynes/cm2) aligned, increased NO, decreased permeability, and showed low proliferation and monocyte adhesion.
• ECs in disturbed flow regions with low shear stress exhibited lack of alignment, reduced NO, and increased proliferation, permeability, and monocyte adhesion.
• ECs in disturbed flow regions exposed to atheroprotective shear stress showed inconsistent alignment and permeability, with persistently low NO levels.

Conclusions:

• The modified parallel plate flow chamber effectively simulates recirculating disturbed flow, aiding the study of hemodynamics' role in EC dysfunction.
• Disturbed flow, particularly at low shear stress, significantly impairs endothelial barrier function and promotes an atherogenic phenotype.
• The study highlights the complex, non-linear relationship between shear stress magnitude, flow patterns, and endothelial cell responses relevant to atherosclerosis.