Exploring the effect of dynamic deformation on the tight junctions of endothelial cells

Abstract Atherosclerosis (Ath) is a leading cause of cardiovascular deaths, accounting for approximately 17.1 million fatalities annually. This condition arises from plaque-induced arterial narrowing, which obstructs blood flow. Traditional animal models face ethical, economic, and translational limitations, while current in vitro models often oversimplify plaque formation by using fixed channels and neglecting the dynamic effects of narrowing on endothelial junctions. The study addresses the limitations by developing a microfluidic device that mimics human-relevant stenosis with dynamic channel narrowing under continuous perfusion. Endothelial cells, which are crucial for maintaining barrier integrity through tight junctions, are subjected to physiological shear stress and hyperlipidaemic conditions by administering free fatty acids. The model evaluates cell alignment, junctional stability, and disease progression under mechanically deformed static conditions. To validate the translational potential of this system, ROS scavenging drug, quercetin is tested for its ability to reverse oxidative stress and barrier dysfunction. This innovative microphysiological system offers a robust platform for investigating endothelial dysfunction in Ath and provides a valuable alternative to animal models for cardiovascular drug testing. By integrating both biochemical and mechanical cues in a controllable environment, this model aims to enhance our understanding of Ath and facilitate the development of more effective therapeutic strategies. Competing Interest Statement The authors have declared no competing interest.