Administration of USP7 inhibitor P22077 inhibited cardiac hypertrophy and remodeling in Ang II-induced hypertensive mice

Hypertension is one of the common causes of pathological cardiac hypertrophy and a major risk for morbidity and mortality of cardiovascular diseases worldwide. Ubiquitin-Specific Protease 7 (USP7), the first identified deubiquitinating enzymes, participated in a variety of biological processes, such as cell proliferation, DNA damage response, tumourigenesis, and apoptosis. However, its role and mechanism in cardiac remodeling remain unclear. Here, our data indicated that USP7 expression was increased during Ang II-induced cardiac hypertrophy and remodeling in mice and humans with heart failure, while the administration of its inhibitor p22077 attenuated cardiac hypertrophy, cardiac fibrosis, inflammation, and oxidase stress. Mechanistically, the administration of p22077 inhibited the multiple signaling pathways, including AKT/ERK, TGF-β/SMAD2/Collagen I/Collagen III, NF-κB/NLRP3, and NAPDH oxidases (NOX2 and NOX4). Taken together, these findings demonstrate that USP7 may be a new therapeutic target for hypertrophic remodeling and HF.

 

Comments：

Hypertension is a significant risk factor for cardiovascular disease, and understanding the molecular mechanisms that contribute to pathological cardiac hypertrophy is crucial for developing new therapeutic approaches.

The research suggests that USP7 expression is increased during Ang II-induced cardiac hypertrophy and remodeling in mice and humans with heart failure. Furthermore, the administration of the USP7 inhibitor p22077 attenuated cardiac hypertrophy, fibrosis, inflammation, and oxidative stress. This suggests that USP7 may play a role in promoting cardiac hypertrophy and remodeling, and that targeting USP7 with an inhibitor like p22077 may have therapeutic potential.

The mechanism by which USP7 inhibition attenuates cardiac remodeling appears to involve inhibition of multiple signaling pathways, including AKT/ERK, TGF-β/SMAD2/Collagen I/Collagen III, NF-κB/NLRP3, and NAPDH oxidases (NOX2 and NOX4). This suggests that USP7 may be involved in multiple pathways that contribute to cardiac hypertrophy and remodeling, and that targeting USP7 may have broad effects on these pathways.

Overall, the findings suggest that USP7 may be a promising therapeutic target for hypertrophic remodeling and heart failure. Further research is needed to fully understand the role of USP7 in these processes and to evaluate the potential of USP7 inhibitors as a therapeutic approach.