Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0162871 (
abdominal aortic aneurysm
)
8,664
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
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.
...
PMID:Brg1 trans-activates endothelium-derived colony stimulating factor to promote calcium chloride induced abdominal aortic aneurysm in mice. 3033 42
