期刊
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
卷 125, 期 -, 页码 6-17出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.yjmcc.2018.10.012
关键词
Brgl; Vascular endothelial cell; Abdominal aortic aneurysm; Transcriptional regulation; Epigenetics
资金
- Natural Science Foundation of China [81725001, 81800426, 81460042, 81770487]
- Haihan Province R&D Fund Key Project [ZDYF2018102]
Endothelial cell derived secretive factors play pivotal roles maintaining the homeostasis by influencing the behaviors of other cells. When dysregulated, these factors may contribute to the disruption of physiological integrity and promote disease genesis in a number of different tissues and organs. In the present study we investigated how targeted deletion of brahma related gene 1 (Brgl), a chromatin remodeling protein, in endothelium might affect the pathogenesis of abdominal aortic aneurysm (AAA) induced by calcium chloride (CaCl2). We report here that compared to the wild type (WT) littermates, endothelial conditional Brgl knockout (ecKO) mice exhibited an attenuated phenotype of AAA. Immunostaining and quantitative PCR analyses showed that vascular inflammation was suppressed in ecKO mice as opposed to WT mice likely due to diminished recruitment of macrophages. Further examination revealed that Brgl deficiency led to a reduction in colony stimulating factor 1 (CSF1) levels. In cultured endothelial cells, Brgl cooperated with histone H3K9 demethylase KDM3A to activate CSF1 transcription and macrophage recruitment thereby perpetuating vascular inflammation. Depletion of BRG1 or KDM3A in endothelial cells dampened CSF1 production and attenuated macrophage chemotaxis. Therefore, our data suggest that epigenetic activation of CSF1 transcription by Brgl may contribute to AAA pathogenesis.
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