Rhodioloside attenuated atherosclerosis progression by inhibiting VCAM-1 gene transcription mediated by p65 activation and CSN5 deubiquitination in endothelial cells

Abstract

Monocyte-endothelial cell adhesion played a pivotal role in the initial stages of Atherosclerosis (AS) progression, exacerbating lipid disturbance and worsening the condition. Rhodioloside (Rho), a renowned compound in traditional Chinese medicine, possesses diverse pharmacological attributes, including anti-inflammatory, antioxidant, anticancer, anti-metabolic dysregulation, and neuroprotective properties. However, the exact mechanism by which Rho exerts its anti-AS effect is still not fully understood. This study aimed to investigate the potential therapeutic benefits of Rho in combating AS. ApoE^−/− mice were fed with a High Fat Diet (HFD) and administered Rho treatment. The investigation evaluated the expression levels of GATA2, CSN5, and VCAM-1 proteins in the endothelium of the aorta. The findings revealed that Rho treatment led to a reduction in the protein expression of GATA2, CSN5, and VCAM-1 in the aortic endothelium, accompanied by decreased phosphorylation of p65. Furthermore, Rho inhibited the ubiquitination of GATA2 and weakened the interaction between PP2Ac and I2PP2A. Additionally, Rho directly suppressed the transcriptional activity of the NF-κB subunit p65 by targeting the I2PP2A-PP2Ac axis.