| First Author | Zhang Y | Year | 2020 |
| Journal | Front Cell Dev Biol | Volume | 8 |
| Pages | 578790 | PubMed ID | 33330454 |
| Mgi Jnum | J:308904 | Mgi Id | MGI:6752723 |
| Doi | 10.3389/fcell.2020.578790 | Citation | Zhang Y, et al. (2020) Brahma-Related Gene 1 Deficiency in Endothelial Cells Ameliorates Vascular Inflammatory Responses in Mice. Front Cell Dev Biol 8:578790 |
| abstractText | 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)-1beta and IL-6, not tumor necrosis factor-alpha (TNF-alpha)] 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-alpha-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. |
