Immune cells and inflammatory mediators cause endothelial dysfunction in a vascular microphysiological system.

Area of Science:

• Cardiovascular Science
• Immunology
• Biomedical Engineering

Background:

• Endothelial dysfunction is a key factor in vascular disorders like hypertension and atherosclerosis.
• Immune system dysregulation, including inflammatory cytokines, contributes to endothelial dysfunction.
• Assessing endothelial function is crucial for understanding vascular health.

Purpose of the Study:

• To evaluate endothelial function using a 3D vascular microphysiological system (MPS).
• To investigate the impact of inflammatory mediators and immune cells on endothelial function.
• To establish a model for cardiovascular disorder research and drug screening.

Main Methods:

• Development of a 3D vascular MPS using human umbilical vein endothelial cells (HUVECs).
• Assessment of endothelial permeability and Ca2+ signaling.
• Exposure of the MPS to inflammatory factors (TNFα, VEGF-A, IL-6) and peripheral blood mononuclear cells (PBMCs).

Main Results:

• Inflammatory mediators disrupted the endothelial barrier and diminished Ca2+ signaling.
• Activated PBMCs significantly increased endothelial permeability and decreased Ca2+ activity.
• The MPS effectively modeled inflammation-induced endothelial dysfunction.

Conclusions:

• The vascular MPS is a valuable tool for studying endothelial dysfunction in cardiovascular diseases.
• Inflammatory mediators and immune cells play critical roles in compromising endothelial barrier integrity and function.
• This model holds promise for screening novel therapeutic interventions.