Impinging flow induces expression of MCP-1 in endothelial cells through activation of the JNK/c-Jun/p38/c-Fos pathway

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. 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 (AP-1), and MCP-1 were detected by western blot, and the messenger RNA (mRNA) expression levels of MCP-1, interleukin (IL)-1β and IL-6 were determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Under impinging flow, the phosphorylation levels of ERK, JNK, and p38, and the protein levels of MCP-1, c-Jun, and c-Fos, increased. The mRNA expression of MCP-1, IL-1β, 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-1β and IL-6, while ERK inhibitors had no obvious effect. Under impinging flow, MCP-1 and inflammatory factors are regulated through the JNK/c-Jun/p38/c-Fos pathway and participate in EC inflammation.