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Ets-1 promotes the progression of cerebral aneurysm by inducing the expression of MCP-1 in vascular smooth muscle cells - PubMed

. 2010 Sep;17(9):1117-23.

doi: 10.1038/gt.2010.60. Epub 2010 Apr 29.

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Ets-1 promotes the progression of cerebral aneurysm by inducing the expression of MCP-1 in vascular smooth muscle cells

T Aoki et al. Gene Ther. 2010 Sep.

Erratum in

  • Gene Ther. 2013 Feb;20(2):235

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.

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