Microfluidic-to-macrofluidic: A simple in vitro model of atherosclerosis induced by fluidic stimulation

Abstract

Atherosclerosis is the narrowing of the arteries due to the formation of fatty plaques, which is the main cause of myocardial infarction and stroke. It is important to develop an in vitro model that can combine multiple-type cell co-culture, vessel wall-like structure, and fluid condition to simulate the processes of atherosclerosis. Herein, we used a simple microfluidic chip made of three polydimethylsiloxane layers to co-culture endothelial and smooth muscle cells in a flat rectangular microchannel. After being connected with a circulating culture medium driven by a peristaltic pump, the flat microchannel was deformed to a tunnel-like macrochannel. The fluid pressure and shear stress applied on the cells in the deformed macrochannel can be varied by adjusting the circulating flow rate and the thickness of the middle layer. Under three levels of the pressure (65, 131, and 196 mm Hg) or shear stress (0.99, 4.78, and 24 dyne/cm2) conditions, a series of atherosclerosis-related events, including endothelial cell junction, pro-inflammatory cytokine secretion, monocyte adhesion, and lipid accumulation, were investigated. The atherosclerosis-related results showed that the medium pressure or shear stress exhibited a relatively weak pro-atherosclerotic effect in a V-shaped trend. To demonstrate the potential in drug screen, the effects of three well-known anti-atherosclerotic drugs (atorvastatin, tetramethylpyrazine, and high-density lipoprotein) on the lipid accumulation and pro-inflammatory cytokine secretion were evaluated under a strong pro-atherosclerotic fluid condition (65 mm Hg, 0.99 dyne/cm2). This in vitro model of atherosclerosis has shown great potential in drug screen application.