title: Ets-1 promotes the progression of cerebral aneurysm by inducing the expression of MCP-1 in vascular smooth muscle cells.
abstract: Cerebral aneurysm (CA) rupture is one of the leading causes of stroke death. Recent experimental studies suggest that the pathophysiology of CA is closely associated with inflammation. A transcription factor, Ets-1, has been shown to regulate vascular inflammation and remodeling in a physiological and pathological condition. The expression and role of Ets-1 in CA development has been investigated in this study. Ets-1 was expressed and activated mainly in vascular smooth muscle cells (VSMCs) in both experimentally induced rat CAs and human CA walls by immunohistochemistry, western blotting and enzyme-linked mobility shift assay. The downstream target of Ets-1 in CA development was identified by chromatin immunoprecipitation (CHIP) analysis. CHIP analysis revealed that Ets-1 transactivated monocyte chemoattractant protein-1 (MCP-1) expression in CA walls. Treatment with ets decoy oligodeoxynucleotides resulted in the prevention of CA enlargement, upregulation of MCP-1 expression and increase in macrophage accumulation in CA walls. In conclusion, Ets-1 mediates MCP-1 expression in VSMCs in CA walls, thus promoting the progression of CAs. Inhibition of DNA-binding activity of Ets-1 may lead to the prevention of human CA enlargement and rupture. Results of this study will provide us a clue to a novel therapeutic strategy for CAs.
authors.affiliation: Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Aoki
authors.forename: H
authors.initials: H
authors.lastname: Kataoka
authors.forename: M
authors.initials: M
authors.lastname: Nishimura
authors.forename: R
authors.initials: R
authors.lastname: Ishibashi
authors.forename: R
authors.initials: R
authors.lastname: Morishita
authors.forename: S
authors.initials: S
authors.lastname: Miyamoto
mesh_terms: D000818:Animals; D018932:Chemokine CCL2 / Q000235:genetics* / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D006801:Humans; D007150:Immunohistochemistry; D002532:Intracranial Aneurysm / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism*; D050784:Proto-Oncogene Protein c-ets-1 / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018932:Chemokine CCL2; D050784:Proto-Oncogene Protein c-ets-1