PMID- 33332775 OWN - NLM STAT- MEDLINE DCOM- 20210915 LR - 20210915 IS - 1582-4934 (Electronic) IS - 1582-1838 (Print) IS - 1582-1838 (Linking) VI - 25 IP - 1 DP - 2021 Jan TI - Sustained expression of MCP-1 induced low wall shear stress loading in conjunction with turbulent flow on endothelial cells of intracranial aneurysm. PG - 110-119 LID - 10.1111/jcmm.15868 [doi] AB - Shear stress was reported to regulate the expression of AC007362, but its underlying mechanisms remain to be explored. In this study, to isolate endothelial cells of blood vessels, unruptured and ruptured intracranial aneurysm (IA) tissues were collected from IA patients. Subsequently, quantitative real-time PCR (qRT-PCR), Western blot and luciferase assay were performed to investigate the relationships between AC007362, miRNAs-493 and monocyte chemoattractant protein-1 (MCP-1) in human umbilical vein endothelial cells (HUVECs) exposed to shear stress. Reduced representation bisulphite sequencing (RRBS) was performed to assess the level of DNA methylation in AC007362 promoter. Accordingly, AC007362 and MCP-1 were significantly up-regulated while miR-493 was significantly down-regulated in HUVECs exposed to shear stress. AC007362 could suppress the miR-493 expression and elevate the MCP-1 expression, and miR-493 was shown to respectively target AC007362 and MCP-1. Moreover, shear stress in HUVECs led to the down-regulated DNA methyltransferase 1 (DNMT1), as well as the decreased DNA methylation level of AC007362 promoter. Similar results were also observed in ruptured IA tissues when compared with unruptured IA tissues. In conclusion, this study presented a deep insight into the operation of the regulatory network of AC007362, miR-493 and MCP-1 upon shear stress. Under shear stress, the expression of AC007362 was enhanced by the inhibited promoter DNA methylation, while the expression of MCP-1 was enhanced by sponging the expression of miR-493. CI - (c) 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd. FAU - Chu, Cheng AU - Chu C AD - Department of Neurology, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China. FAU - Xu, Gang AU - Xu G AD - Department of Neurology, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China. FAU - Li, Xiaocong AU - Li X AD - Department of Neurology, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China. FAU - Duan, Zuowei AU - Duan Z AD - Department of Neurology, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China. FAU - Tao, Lihong AU - Tao L AD - Department of Neurology, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China. FAU - Cai, Hongxia AU - Cai H AD - Department of Neurology, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China. FAU - Yang, Ming AU - Yang M AD - Department of Neurology, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China. FAU - Zhang, Xinjiang AU - Zhang X AD - Department of Neurology, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China. FAU - Chen, Bin AU - Chen B AD - Department of Neurology, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China. FAU - Zheng, Yanyu AU - Zheng Y AD - Department of Neurology, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China. FAU - Shi, Hongcan AU - Shi H AUID- ORCID: 0000-0003-2228-4828 AD - Department of Neurology, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China. FAU - Li, Xiaoyu AU - Li X AD - Department of Pathophysiology, Key Laboratory of Cardiovascular Disease and Molecular Intervention, Nanjing Medical University, Nanjing, China. LA - eng GR - YZ2017111/Yangzhou Natural Science Foundation-Youth Fund Project/ PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20201217 PL - England TA - J Cell Mol Med JT - Journal of cellular and molecular medicine JID - 101083777 RN - 0 (Chemokine CCL2) RN - 0 (MIRN493 microRNA, human) RN - 0 (MicroRNAs) SB - IM MH - Base Sequence MH - Chemokine CCL2/genetics/*metabolism MH - DNA Methylation/genetics MH - Female MH - Human Umbilical Vein Endothelial Cells/metabolism/*pathology MH - Humans MH - Intracranial Aneurysm/genetics/*pathology MH - Male MH - MicroRNAs/genetics/metabolism MH - Middle Aged MH - Promoter Regions, Genetic/genetics MH - *Rheology MH - *Stress, Mechanical MH - Up-Regulation/genetics PMC - PMC7810920 OTO - NOTNLM OT - IA OT - MCP-1 OT - miRNA OT - shear stress COIS- None. EDAT- 2020/12/18 06:00 MHDA- 2021/09/16 06:00 PMCR- 2021/01/01 CRDT- 2020/12/17 17:22 PHST- 2020/04/19 00:00 [received] PHST- 2020/07/30 00:00 [revised] PHST- 2020/08/24 00:00 [accepted] PHST- 2020/12/18 06:00 [pubmed] PHST- 2021/09/16 06:00 [medline] PHST- 2020/12/17 17:22 [entrez] PHST- 2021/01/01 00:00 [pmc-release] AID - JCMM15868 [pii] AID - 10.1111/jcmm.15868 [doi] PST - ppublish SO - J Cell Mol Med. 2021 Jan;25(1):110-119. doi: 10.1111/jcmm.15868. Epub 2020 Dec 17.