Department of Nanoscience and Nanoengineering, Istanbul Technical University, 34469, Istanbul, Turkey.
Nanotechnology Research and Application Center-ITUnano, Istanbul Technical University, 34469, Istanbul, Turkey.
Sci Rep. 2021 Jul 13;11(1):14379. doi: 10.1038/s41598-021-93935-w.
Atherosclerosis is a long-term disease process of the vascular system that is characterized by the formation of atherosclerotic plaques, which are inflammatory regions on medium and large-sized arteries. There are many factors contributing to plaque formation, such as changes in shear stress levels, rupture of endothelial cells, accumulation of lipids, and recruitment of leukocytes. Shear stress is one of the main factors that regulates the homeostasis of the circulatory system; therefore, sudden and chronic changes in shear stress may cause severe pathological conditions. In this study, microfluidic channels with cavitations were designed to mimic the shape of the atherosclerotic blood vessel, where the shear stress and pressure difference depend on design of the microchannels. Changes in the inflammatory-related molecules ICAM-1 and IL-8 were investigated in THP-1 cells in response to applied shear stresses in an continuous cycling system through microfluidic channels with periodic cavitations. ICAM-1 mRNA expression and IL-8 release were analyzed by qRT-PCR and ELISA, respectively. Additionally, the adhesion behavior of sheared THP-1 cells to endothelial cells was examined by fluorescence microscopy. The results showed that 15 Pa shear stress significantly increases expression of ICAM-1 gene and IL-8 release in THP-1 cells, whereas it decreases the adhesion between THP-1 cells and endothelial cells.
动脉粥样硬化是血管系统的一种长期疾病过程,其特征是形成动脉粥样硬化斑块,这是中大型动脉的炎症区域。有许多因素促成斑块的形成,例如剪切应力水平的变化、内皮细胞破裂、脂质积累和白细胞募集。剪切应力是调节循环系统内稳态的主要因素之一;因此,剪切应力的突然和慢性变化可能导致严重的病理状况。在这项研究中,设计了带有空化的微流控通道来模拟动脉粥样硬化血管的形状,其中剪切应力和压差取决于微通道的设计。通过周期性空化的微流控通道,在连续循环系统中研究了施加于 THP-1 细胞的剪切应力对炎症相关分子 ICAM-1 和 IL-8 的影响。通过 qRT-PCR 和 ELISA 分别分析 ICAM-1 mRNA 表达和 IL-8 释放。此外,通过荧光显微镜检查了剪切 THP-1 细胞与内皮细胞的粘附行为。结果表明,15 Pa 的剪切应力显著增加了 THP-1 细胞中 ICAM-1 基因的表达和 IL-8 的释放,而降低了 THP-1 细胞与内皮细胞之间的粘附。