Brg1 trans-activates endothelium-derived colony stimulating factor to promote calcium chloride induced abdominal aortic aneurysm in mice

Xinjian Zhang, Shuai Liu, Xinyu Weng, Teng Wu, Liming Yu, Yong Xu, Junli Guo

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

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 (Brg1), a chromatin remodeling protein, in endothelium might affect the pathogenesis of abdominal aortic aneurysm (AAA) induced by calcium chloride (CaCl 2 ). We report here that compared to the wild type (WT) littermates, endothelial conditional Brg1 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 Brg1 deficiency led to a reduction in colony stimulating factor 1 (CSF1) levels. In cultured endothelial cells, Brg1 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 Brg1 may contribute to AAA pathogenesis.

Original languageEnglish (US)
Pages (from-to)6-17
Number of pages12
JournalJournal of Molecular and Cellular Cardiology
Volume125
DOIs
StatePublished - Dec 2018
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported, in part, by grants from the Natural Science Foundation of China ( 81725001 , 81800426 , 81460042 , 81770487 ) and Haihan Province R&D Fund Key Project ( ZDYF2018102 ).

Keywords

  • Abdominal aortic aneurysm
  • Brg1
  • Epigenetics
  • Transcriptional regulation
  • Vascular endothelial cell

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't

Fingerprint Dive into the research topics of 'Brg1 trans-activates endothelium-derived colony stimulating factor to promote calcium chloride induced abdominal aortic aneurysm in mice'. Together they form a unique fingerprint.

Cite this