# Rosuvastatin Upregulates RCOR1 to Repress C10ORF10 Transcription and Alleviate Oxidative Stress and Plaque Formation in Atherosclerosis

## TL;DR

Rosuvastatin reduces atherosclerosis by boosting RCOR1, which suppresses C10ORF10 and lowers oxidative stress and plaque buildup.

## Contribution

Identifies RCOR1 as a novel mediator of RVS's anti-atherosclerotic effects through repression of C10ORF10 transcription.

## Key findings

- RVS lowers cholesterol and oxidative stress in atherosclerotic mice.
- RCOR1 upregulation by RVS represses C10ORF10 transcription, reducing plaque formation.
- Silencing RCOR1 or C10ORF10 alters RVS's protective effects in mice and cells.

## Abstract

Rosuvastatin (RVS) is an HMG‐CoA reductase inhibitor with lipid‐lowering properties. This study aims to investigate the role of RVS in plaque formation in atherosclerosis (AS) and its functional mechanism. ApoE−/− mice were fed a high‐fat diet to generate a mouse model of AS. RVS treatment reduced serum levels of total cholesterol, triglycerides, and low‐density lipoprotein cholesterol in atherosclerotic mice, alleviated oxidative stress, and ameliorated lipid deposition, plaque formation, and fibrosis in the mouse aortic tissues. In vitro, it reduced reactive oxygen species and suppressed the proliferation and migration of oxidized low‐density lipoprotein‐challenged human vascular smooth muscle cells (HVSMCs). REST corepressor 1 (RCOR1) was identified as a target protein upregulated by RVS. It was found to repress transcription of decidual protein induced by progesterone 1 (DEPP1/C10ORF10) by binding to its promoter. Silencing of RCOR1 negated the AS‐ameliorating effects of RVS in mice and HVSMCs. However, the AS‐like symptoms in mice and HVSMC activity were suppressed by the additional C10ORF10 silencing. In conclusion, this study demonstrates that RVS alleviates oxidative stress and reduces atherosclerotic plaque formation by increasing RCOR1‐mediated transcriptional repression of C10ORF10.