Abstract
Although a variety of animal models of atherosclerosis have been developed, these models are time-consuming and costly. Here, we describe an in vitro model to induce foam cell formation in the early stage of atherosclerosis. This model is based on a three-dimension co-culture system in a stretchable microfluidic device. An elastic membrane embedded in the microfluidic device is capable of delivering nonuniform strain to vascular smooth muscle cells, endothelial cells and monocytes adhering thereto, which are intended to mimic the biological environment of blood vessels. Under low-density lipoprotein and stretch treatment, foam cell formation was successfully induced in co-culture with changes in mRNA and protein expression of some related key factors. Subsequently, the model was used to assess the inhibitory effect of atorvastatin on foam cell formation. The results obtained indicate that atorvastatin has a significantly dose-dependent inhibition of foam cell formation, which can be explained by the changes in mRNA and protein expression of the related factors. In principle, the model can be used to study the role of different types of cells in the formation of foam cells, as well as the evaluation of anti-atherosclerotic drugs.
Highlights
Atherosclerosis, a chronic cardiovascular disease, is mainly caused by hyperlipidemia, hypertension, and diabetes[1,2]
From a physiological point of view, vascular smooth muscle cells (VSMCs), endothelial cells (ECs) and monocytes are three types of the main cells involved in atherosclerosis; it is preferable to establish a co-culture system including these cells for studying foam cell formation
Shear stress generated by blood flow is anti-atherogenic, while circumferential stretch caused by hydrostatic pressure is pro-atherogenic
Summary
Atherosclerosis, a chronic cardiovascular disease, is mainly caused by hyperlipidemia, hypertension, and diabetes[1,2]. If the above-mentioned cholesterol homeostasis is disturbed, excessive cholesterol ester or free cholesterol will be accumulated, thereby causing foam cell formation or cell necrosis. From a physiological point of view, vascular smooth muscle cells (VSMCs), endothelial cells (ECs) and monocytes are three types of the main cells involved in atherosclerosis; it is preferable to establish a co-culture system including these cells for studying foam cell formation. Several studies on the effect of shear stress on vascular endothelial cells have been reported[21,22,23,24,25], few of them are able to simulate disturbed shear stress and uneven circumferential stretch of atherosclerosis-prone site. We used a stretchable microfluidic device to induce foam cell formation under LDL and stretching treatment, and applied it for evaluating the efficacy of atorvastatin to inhibit foam cell formation
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