BRD4 Silencing Protects Angiotensin II-Induced Cardiac Hypertrophy by Inhibiting TLR4/NF-κB and Activating Nrf2-HO-1 Pathways. (19th September 2022)

• Record Type: Journal Article
• Authors: Fang, Ming; Luo, Jun; Zhu, Xi; Wu, Yingbiao; Li, Xinming
• Other Names: Ali Sheikh Md Sayed Academic Editor.
• Is Part Of: Cardiology research and practice. Volume 2022(2022)
• Publication Date: 2022-09-19
• Subjects: Cardiology -- Research -- Periodicals; Cardiology -- Periodicals; Cardiology; Cardiology; Cardiology -- Research; Electronic journals; Periodicals; Periodicals; 616.12
• DOI: 10.1155/2022/8372707
• Languages: English
• ISSNs: 2090-8016

Abstract

Abstract : Background . Heart failure is a critical health problem worldwide, and cardiac hypertrophy is an important characteristic of heart failure. Bromodomain-containing protein 4 (BRD4) is involved in various cellular processes, including cardiac hypertrophy. This study aimed to investigate the mechanism underlying the effects of BRD4 on cardiac hypertrophy. Methods . Rat myoblast H9c2 cells were treated with angiotensin II (Ang II) to increase the mRNA and protein expressions of BRD4. BRD4 was silenced by small interfering RNA (siRNA) in H9c2 cells. Proteins involved in Nrf2-HO-1 pathway were determined by Western blot. Results . Our data suggest that BRD4 silencing attenuated Ang II, increased the percentage of TUNEL + cells and caspase-3 activity, increased oxidative stress, and increased the expression and content of pro-inflammatory cytokines. Mechanistically, we found that BRD4 silencing enhanced the protein expressions of Nrf2 and HO-1 and inhibited the TLR4 and phosphorylation of NF-kappa B in Ang II-stimulated H9c2 cells. TLR4 overexpression attenuated cardioprotection against Ang II by BRD4 silencing, including cardiac hypertrophy, oxidative stress, and inflammatory cytokine production. Additionally, TLR4 overexpression attenuated an increase in Nrf2 and HO-1 proteins and decreased phosphorylated NF-kappa B in H9c2 cells. Conclusion . Our results speculate that the BRD4/TLR4 axis might be a promising strategy for treating cardiovascular diseases with cardiac hypertrophy, including HF.