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

Yuanyuan Zhang; Huidi Wang; Mingzi Song; Tongchang Xu; Xuyang Chen; Tianfa Li; Teng Wu

doi:10.3389/fcell.2020.578790

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

Front Cell Dev Biol. 2020 Nov 30:8:578790. doi: 10.3389/fcell.2020.578790. eCollection 2020.

Authors

Yuanyuan Zhang¹, Huidi Wang², Mingzi Song³, Tongchang Xu², Xuyang Chen², Tianfa Li¹, Teng Wu²

Affiliations

¹ Department of Cardiology, The First Affiliated Hospital of Hainan Medical University, Haikou, China.
² Key Laboratory of Targeted Intervention of Cardiovascular Disease, Department of Pathophysiology, Collaborative Innovation Center for Cardiovascular Translational Medicine, Nanjing Medical University, Nanjing, China.
³ Laboratory Center for Experimental Medicine, Jiangsu Health Vocational College, Nanjing, China.

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 ^-/- ; BRG1 ^fl/fl ) littermates, endothelium conditional BRG1 knockout mice (CKO, ApoE ^-/- ; BRG1 ^fl/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.

Keywords: BRG1; abdominal aortic aneurysms; diabetic atherosclerosis; endothelium; inflammation.