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Brahma-Related Gene 1 Deficiency in Endothelial Cells Ameliorates Vascular Inflammatory Responses in Mice

Authors :
Yuanyuan Zhang
Huidi Wang
Mingzi Song
Tongchang Xu
Xuyang Chen
Tianfa Li
Teng Wu
Source :
Frontiers in Cell and Developmental Biology, Vol 8 (2020)
Publication Year :
2020
Publisher :
Frontiers Media S.A., 2020.

Abstract

Endothelial dysfunction plays an important role in promoting the progression of disease genesis such as atherosclerosis and abdominal aortic aneurysm (AAA). The physiological unbalance of endothelial cells is a major pathological basis. In this present study, we investigated Brahma-related gene 1 (BRG1), a chromatin remodeling protein, was in mouse models of diabetic atherosclerosis and AAA, focusing on its role in endothelial dysfunction. We report that compared with their wild-type (WT, ApoE–/–; BRG1fl/fl) littermates, endothelium conditional BRG1 knockout mice (CKO, ApoE–/–; BRG1fl/fl; CDH5-cre) exhibited an alleviated phenotype of diabetic atherosclerosis. Immunohistochemically staining and real-time PCR analysis demonstrated fewer macrophages recruitment with a reduction of vascular inflammatory in CKO mice compared with WT mice. Further research in the Ang-II induced AAA model revealed that BRG1 deficiency had the protective effects on endothelium conditional BRG1 deletion, evidenced by the downregulation of pro-inflammatory mediators [interleukin (IL)-1β and IL-6, not tumor necrosis factor-α (TNF-α)] in the vessels of CKO mice compared with WT mice. In Ea.hy926 cell lines, anti-BRG1 small interfering RNA and PFI-3 treatment obviously alleviated tumor necrosis factor-α-induced IL-6 and CCL2 expression, and further research demonstrated that the BRG1 inhibition in endothelial cells not only decreased c-Fos expression but also blocked the c-Fos translocation into nuclei. In conclusion, our results suggest that endothelial BRG1 deficiency may protect the mice from diabetic atherosclerosis and AAA via inhibiting inflammatory response in vessels.

Details

Language :
English
ISSN :
2296634X
Volume :
8
Database :
Directory of Open Access Journals
Journal :
Frontiers in Cell and Developmental Biology
Publication Type :
Academic Journal
Accession number :
edsdoj.6f8fccd04da843d9bbf76212b39f6583
Document Type :
article
Full Text :
https://doi.org/10.3389/fcell.2020.578790