Engineered endothelium model enables recapitulation of vascular function and early atherosclerosis development

Area of Science:

• Biomedical Engineering
• Vascular Biology
• Pathology Modeling

Background:

• The vascular endothelium is crucial for human health.
• Existing models often lack the complexity to fully represent endothelial function and disease.
• A physiologically relevant model is needed for advanced vascular studies.

Purpose of the Study:

• To develop a novel engineered endothelium model (EEM).
• To assess the EEM's ability to recapitulate normal vascular function.
• To evaluate the EEM's capacity for modeling early vascular pathology, specifically atherosclerosis.

Main Methods:

• Fabrication of an artificial basement membrane (aBM) integrating polyvinyl alcohol hydrogel and decellularized extracellular matrix.
• Co-culture of endothelial cells (ECs) and pericytes (PCs) on the aBM.
• Assessment of barrier integrity, cell junction formation (VE-cadherin), nitric oxide (NO) secretion, and foam cell formation.

Main Results:

• The EEM formed robust adherens junctions and an impermeable barrier, secreting nitric oxide (NO).
• Endothelial cells and pericytes interaction via aBM promoted hemoglobin alpha 1 (Hb-α1) development, linked to NO control.
• The EEM demonstrated resilience under inflammation and successfully recapitulated key events of atherosclerotic foam cell formation.

Conclusions:

• The engineered endothelium model (EEM) effectively mimics both normal vascular endothelium and early pathological conditions.
• The EEM provides a physiologically relevant platform for vascular research and disease modeling, particularly for atherosclerosis.
• This model facilitates the study of endothelial cell interactions and responses in health and disease states.