Abstract
Atherosclerosis is a significant cause of mortality and morbidity. Studies suggest that the chemokine receptor CX3CR1 plays a critical role in atherogenesis. Shear stress is an important mechanical force that affects blood vessel function. In this study, we investigated the effect of shear stress on CX3CR1 expression in vascular endothelial cells (VECs). First, cells were exposed to different shear stress and then CX3CR1 mRNA and protein were measured by quantitative RT-PCR and western blot analysis, respectively. CX3CR1 gene silencing was used to analyze the molecular mechanisms underlying shear stress-mediated effects on CX3CR1 expression. CX3CR1 mRNA and protein expression were significantly increased with 4.14 dyne/cm2 of shear stress compared with other tested levels of shear stress. We observed a significant increase in CX3CR1 mRNA levels at 2 h and CX3CR1 protein expression at 4 h. CX3CR1-induced VCAM-1 expression in response to low shear stress by activating NF-κB signaling pathway in VECs. Our findings demonstrate that low shear stress increases CX3CR1 expression, which increases VCAM-1 expression due to elevated NF-κB activation. The current study provides evidence of the correlation between shear stress and atherosclerosis mediated by CX3CR1.
Highlights
Atherosclerosis, a disease that causes arteriostenosis due to plaque formation, is a leading cause of morbidity and mortality
When vascular endothelial cells (VECs) are continuously exposed to blood flow, they are subjected to different degrees of shear stress, including laminar shear stress and disturbed flow, which can affect endothelial cell function [22, 23]
This study provides evidence that low shear stress increased CX3CR1 expression in VECs, which resulted in an increase in VCAM-1 through NF-κB signaling
Summary
Atherosclerosis, a disease that causes arteriostenosis due to plaque formation, is a leading cause of morbidity and mortality. Risk factors, such as hypertension and diabetes, lead to vascular endothelial cell (VEC) dysfunction throughout the vasculature [1, 2], atherosclerosis. Inflammation plays a primary role in atherogenesis, and numerous studies have shown that the inflammatory response is a key factor in the progression of atherosclerosis in vascular disease [5]. VCAM-1 is an important adhesion molecule involved in inflammation [19] and its expression on the vascular endothelium can be increased by pro-inflammatory cytokines [20]. The results indicate that low shear stress upregulates CX3CR1 expression, which subsequently induces VCAM-1 expression downstream of NF-κB activation in VECs
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