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

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.

Epigenetic Repression of Chloride Channel Accessory 2 Transcription in Cardiac Fibroblast: Implication in Cardiac Fibrosis

“…Whole cell lysates were obtained by re-suspending cell pellets in RIPA buffer (50 mM Tris pH7.4, 150 mM NaCl, 1% Triton X-100) with freshly added protease inhibitor (Roche) as previously described ( Chen et al, 2020a , b , c ; Wu X. et al, 2020 ; Yang et al, 2020b ; Zhang et al, 2020 ; Chen B. et al, 2021 ; Dong et al, 2021 ). Nuclear proteins were extracted using the NE-PER Kit (Pierce) following manufacturer’s recommendation.…”

“…RNA was extracted with the RNeasy RNA isolation kit (Qiagen). Reverse transcriptase reactions were performed using a SuperScript First-strand Synthesis System (Invitrogen) as previously described ( Dong et al, 2020 ; Hong et al, 2020 ; Wu T. et al, 2020 ; Yang et al, 2020a , b , 2021 ; Zhang et al, 2020 ; Kong et al, 2021b ). Real-time PCR reactions were performed on an ABI Prism 7500 system.…”

A GSK3-SRF Axis Mediates Angiotensin II Induced Endothelin Transcription in Vascular Endothelial Cells

“…RNA was extracted with the RNeasy RNA isolation kit (Qiagen, Hilden, Germany). Reverse transcriptase reactions were performed using a SuperScript First-strand Synthesis System (Invitrogen, Waltham, MA, United States) as previously described ( Zhang et al, 2020 ; Liu et al, 2021 ). Real-time PCR reactions were performed on an ABI Prism 7500 system with the following primers: ET1 , 5′-AGAGTGTGTCTACTTCTGCCA-3′ and 5′-CTTCCAAGTCCATACGGAACAA-3′; GSK3B, 5′-GG CAGCATGAAAGTTAGCAGA-3′ and 5′-GGCGACCAGT TCTCCTGAATC-3′.…”

HES5-mediated repression of LIGHT transcription may contribute to apoptosis in hepatocytes

“…Whole-cell lysates were extracted by re-suspending the cell pellet in RIPA buffer (50 mM Tris pH 7.4, 150 mM NaCl, 1% NP40, 0.5% sodium deoxycholate, 0.1% SDS) with freshly added protease inhibitor tablet (Thermo Fisher) as previously described [ 59 – 66 ]. Specific antibodies or pre-immune IgGs (P.I.I.)…”