Low shear stress induces inflammatory response via CX3CR1/NF-ΚB signal pathway in human umbilical vein endothelial cells

Low shear stress (LSS) has been reported to induce atherosclerosis. However, the molecular mechanisms un-derlying inflammation induced by LSS are still poorly understood. The objective of our study is the compre-hensive identification of molecular circuitry involved in low shear stress-induced inflammation in human umbilical vein endothelial cells (HUVECs) through protein profiling and cell function experiment. In this study, Western blotting analyses revealed a significant increase in the expression of CX3CR1, nucleusP65, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and Interleukin-6 (IL-6), while the expression of cytosolic P65 and I kappa B has significantly decreased in HUVECs treated with low shear stress. CX3CR1 Sh-RNA was use to reveal its effect on LSS-induced inflammation. Further, specific NF-kappa B P65 inhibitors pyr-rolidinedithiocarbamate (PDTC) were used to reveal the downstream NF-kappa B P65 exclusively involved in LSS-induced inflammation in HUVECs, this effect can be abrogated by CX3CR1 sh-RNA and NF-kappa B inhibitors. Monocyte adhesion assay and scratch test revealed low shear stress to promotes adhesion of monocytes and migration of cells, this effect can be abrogated by CX3CR1 sh-RNA and NF-kappa B inhibitors. LSS was involved in the expression of adhesion molecules and chemokines, which are important for the initiation of endothelial inflammation-related atherosclerosis. Therefore, the cell signaling pathways activated by LSS in endothelial cells may represent therapeutic targets of atherosclerosis.

Automated summary

Low shear stress (LSS) can induce the development of atherosclerosis, but the molecular mechanisms of LSS-induced inflammation are still unclear. This study comprehensively identified the molecular circuitry involved in LSS-induced inflammation in human umbilical vein endothelial cells (HUVECs) through protein profiling and cell function experiments. The results showed that LSS increased the expression of CX3CR1, nucleusP65, ICAM-1, VCAM-1, and IL-6, while decreasing the expression of cytosolic P65 and I kappa B in HUVECs. CX3CR1 sh-RNA and NF-kappa B inhibitors could abrogate the effect of LSS-induced inflammation. Monocyte adhesion assay and scratch test revealed that LSS promotes monocyte adhesion and cell migration, which can be reversed by CX3CR1 sh-RNA and NF-kappa B inhibitors. This study suggests that the signaling pathways activated by LSS in endothelial cells may serve as therapeutic targets for atherosclerosis.