A microfluidic model to study the effects of arrhythmic flows on endothelial cells

Area of Science:

• Cardiovascular Biology
• Biomedical Engineering
• Cellular Mechanobiology

Background:

• Atrial fibrillation (AF) is a common arrhythmia linked to cardiovascular events.
• Endothelial dysfunction is implicated in AF-related cardiovascular risks.
• Current in vitro models inadequately replicate arrhythmic flow for endothelial cell studies.

Purpose of the Study:

• To develop and utilize a novel microfluidic system to investigate the effects of arrhythmic blood flow on human aortic endothelial cells (HAECs).
• To systematically analyze how variations in pulse frequency, amplitude, and shear stress influence endothelial cell mechanobiology under AF conditions.

Main Methods:

• Development of a microfluidic device with a computer-controlled piezoelectric pump to generate controlled arrhythmic flow.
• Modulation of flow rate to mimic physiological and pathophysiological shear stress levels.
• Assessment of endothelial cell morphology, beta-catenin distribution, and inflammatory markers (ICAM-1) in response to simulated AF flow.

Main Results:

• Arrhythmic flow at physiological shear stress induced endothelial cell spreading and altered beta-catenin distribution.
• Low and atherogenic shear stress levels under arrhythmic flow did not promote cell spreading or beta-catenin redistribution.
• Arrhythmic flow, regardless of shear stress level, increased monocyte adhesion via ICAM-1 upregulation, indicating inflammation.

Conclusions:

• The developed microfluidic system effectively simulates arrhythmic flow conditions for studying endothelial cell mechanobiology.
• Arrhythmic flow's impact on endothelial cells is dependent on shear stress levels, affecting cell morphology and beta-catenin.
• Arrhythmic flow consistently promotes endothelial inflammation, suggesting a key mechanism in AF-related cardiovascular pathology.