Endothelial cell response to biomechanical forces under simulated vascular loading conditions

Area of Science:

• Biomedical Engineering
• Cell Biology
• Cardiovascular Research

Background:

• Endothelial cells (EC) in vivo experience constant hemodynamic forces (HF) including pressure and shear stress.
• Understanding EC response to these forces is crucial for cardiovascular health and disease research.
• Existing in vitro models often fail to replicate the complex biomechanical environment accurately.

Purpose of the Study:

• To design, create, and validate a novel perfusion bioreactor.
• To apply controlled shear stress and intravascular pressure to endothelial cells in vitro.
• To characterize endothelial cell morphology, orientation, and gene expression under simulated HF.

Main Methods:

• Development of a novel perfusion bioreactor system.
• Culturing endothelial cells on a non-compliant silicone tube.
• Application of dual biomechanical conditioning: pressure (120/60 mmHg) and low shear stress (5 dyn/cm^2).
• Analysis of endothelial cell morphology, F-actin organization, and gene expression (E-selectin).

Main Results:

• Endothelial cells exhibited time-dependent elongation and realignment oblique to shear stress.
• F-actin microfilaments reorganized into dense stress fibers perpendicular to flow.
• Combinatorial biomechanical conditioning induced expression of the inflammatory marker E-selectin.

Conclusions:

• The novel bioreactor effectively simulates in vivo hemodynamic forces on endothelial cells.
• Simulated biomechanical conditioning alters endothelial cell morphology, cytoskeletal organization, and inflammatory gene expression.
• This model provides a valuable tool for studying endothelial cell mechanobiology and inflammatory responses.