OC 10.4 - Bioengineered Vascular Model of Foam Cell Formation

Background: Foam cell formation is a multistep and sequential biological process, which ultimately disrupt the integrity of both the endothelial and subendothelial layers within the vessel. It serves as the underlying cause of various cardiovascular diseases, contributing to their development and progression. Cardiovascular disease remains to be the leading cause of death worldwide. Hence, there is a continuous need to use multidisciplinary approaches to identify new therapeutic targets.

Aims: To deepen our understanding of the development and progress of cardiovascular diseases, it is important to create models that recapitulate foam cell formation. Considering the high cost and complexity of in vivo models, we aimed to generate an in vitro system.

Methods: Using microfluidic technology, we generated a blood vessel model which incorporates a three-dimensional extracellular matrix and an endothelial covered lumen. This model allowed us to perform experiments under the pathophysiological hemodynamic recapitulating the complexities of the native vascular regions.

Results: Using this model, we studied the effectors that regulate monocyte adhesion and migration as well as foam cell formation inside the bioengineered model of blood vessel. We found that peripheral blood mononuclear cells (PBMCs) adhesion and migration are regulated by both the endothelium and the monocytes themselves. PBMCs only migrated into the extracellular matrix when endothelial cells were cultured in the vessel wall. In addition, the exposure of endothelial cells to TNF-α or low shear stress increased PBMCs migration into the subendothelial matrix, demonstrating the critical role of endothelial cells in initiating and guiding monocyte adhesion and migration. Pre exposure of PBMCs to high shear stress also increased PBMCs adhesion and migration but did not affect their capacity to form foam cells.

Conclusion(s): Our versatile model allows for mechanistic studying of foam cell formation under tailored conditions and with the potential to accelerates the drug discovery process of cardiovascular diseases.