An in vitro microfluidic model of the human cardiovascular system for use in pharmaceutical screening applications

WC12 2023 -- Cardiovascular disease is the leading cause of death worldwide; however, no regulatory assays are currently available to predict drug/chemical-linked effects on atherosclerosis (an inflammatory process involving a series of progressive cellular events, including monocyte adhesion to the luminal endothelial surface). We have developed an in vitro cardiovascular adhesion assay using commercially available BioFlux? microfluidic technology to model monocyte adhesion to primary human aortic endothelial cells (HAECs), mimicking an important early stage of atherosclerosis and predictive of in vivo inflammatory outcomes. We generated pilot data to establish assay sensitivity for detection of pro- or anti-inflammatory effects of 20 blinded chemical, pharmaceutical or food compounds on the endothelium. Monocyte adhesion to HAECs was evaluated and mechanistically linked to modulation of cytokine release in response to known inflammatory mediators. This work demonstrates an in vitro endpoint for screening and preclinical assessment as a predictor of atherosclerotic risk. Using this technology, we have developed pilot data for an in vitro assay with physiological relevance that creates a bridge between in vitro and in vivo experiments.