PMID- 35580782 OWN - NLM STAT- MEDLINE DCOM- 20220810 LR - 20220830 IS - 1878-8769 (Electronic) IS - 1878-8750 (Linking) VI - 164 DP - 2022 Aug TI - 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. PG - e681-e693 LID - S1878-8750(22)00663-5 [pii] LID - 10.1016/j.wneu.2022.05.032 [doi] AB - 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)-1beta, 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-1beta, 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-1beta, 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. CI - Copyright (c) 2022 Elsevier Inc. All rights reserved. FAU - Zhu, Huaxin AU - Zhu H AD - Department of Neurosurgery, the First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China. FAU - Hao, Zheng AU - Hao Z AD - Department of Neurosurgery, the First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China; Trauma Center, the First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China. FAU - Xing, Zelong AU - Xing Z AD - Department of Neurosurgery, the First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China; Department of Neurosurgery, Jiujiang University Affiliated Hospital, Jiujiang, Jiangxi, China. FAU - Tan, Jiacong AU - Tan J AD - Department of Neurosurgery, the First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China. FAU - Zhao, Yeyu AU - Zhao Y AD - Department of Neurosurgery, the First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China. FAU - Li, Meihua AU - Li M AD - Department of Neurosurgery, the First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China. Electronic address: limeihua2000@sina.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220514 PL - United States TA - World Neurosurg JT - World neurosurgery JID - 101528275 RN - 0 (Chemokine CCL2) RN - 0 (Interleukin-6) RN - 0 (RNA, Messenger) RN - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases) RN - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases) SB - IM MH - Cells, Cultured MH - *Chemokine CCL2/genetics/metabolism MH - Extracellular Signal-Regulated MAP Kinases MH - Human Umbilical Vein Endothelial Cells MH - Humans MH - Interleukin-6/metabolism MH - *JNK Mitogen-Activated Protein Kinases/metabolism MH - RNA, Messenger/metabolism OTO - NOTNLM OT - HUVECs OT - Hemodynamics OT - JNK OT - MCP-1 OT - p38 EDAT- 2022/05/18 06:00 MHDA- 2022/08/11 06:00 CRDT- 2022/05/17 19:25 PHST- 2022/05/04 00:00 [received] PHST- 2022/05/09 00:00 [accepted] PHST- 2022/05/18 06:00 [pubmed] PHST- 2022/08/11 06:00 [medline] PHST- 2022/05/17 19:25 [entrez] AID - S1878-8750(22)00663-5 [pii] AID - 10.1016/j.wneu.2022.05.032 [doi] PST - ppublish SO - World Neurosurg. 2022 Aug;164:e681-e693. doi: 10.1016/j.wneu.2022.05.032. Epub 2022 May 14.