Impinging Flow Induces Expression of Monocyte Chemoattractant Protein-1 in Endothelial Cells Through Activation of the c-Jun N-terminal Kinase/c-Jun/p38/c-Fos Pathway.

ABSTRACT

OBJECTIVE: Monocyte chemoattractant protein-1 (MCP-1) is an important regulator of the formation and development of intracranial aneurysms. This study explored the molecular mechanisms underlying the induction of MCP-1 and related inflammatory factors in human umbilical vein endothelial cells (HUVECs) under hemodynamic conditions. METHODS: A modified T chamber was used to simulate fluid flow at the bifurcation of the artery and wall shear stress on HUVECs in vitro. Changes in HUVECs were analyzed in response to impinging flow. And HUVECs without impinging flow were used as the control group. Protein expression levels of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), p38, activator protein-1, and MCP-1 were detected by Western blot, and the messenger RNA expression levels of MCP-1, interleukin (IL)-1ß, and IL-6 were determined by quantitative reverse transcription polymerase chain reaction. RESULTS: Under impinging flow, the phosphorylation levels of ERK, JNK, and p38, as well as the protein levels of MCP-1, c-Jun, and c-Fos, increased. The messenger RNA expression of MCP-1, IL-1ß, and IL-6 also increased in HUVECs. Pretreatment of the HUVECs with inhibitors of JNK and p38 significantly attenuated the increased expression of MCP-1, IL-1ß, and IL-6, while ERK inhibitors had no obvious effect. CONCLUSIONS: Under impinging flow, MCP-1 and inflammatory factors are regulated through the JNK/c-Jun/p38/c-Fos pathway and participate in EC inflammation.