Rosuvastatin Upregulates RCOR1 to Repress C10ORF10 Transcription and Alleviate Oxidative Stress and Plaque Formation...

Area of Science:

• Cardiovascular Biology
• Pharmacology
• Molecular Medicine

Background:

• Atherosclerosis (AS) involves plaque formation driven by lipid dysregulation and oxidative stress.
• Statins, like Rosuvastatin (RVS), are known for their lipid-lowering effects.
• The precise molecular mechanisms of RVS in AS plaque progression require further elucidation.

Purpose of the Study:

• To investigate the role of Rosuvastatin (RVS) in mitigating atherosclerosis plaque formation.
• To elucidate the functional mechanism of RVS in the context of AS.
• To identify RVS-modulated molecular targets involved in AS pathogenesis.

Main Methods:

• ApoE^-/- mice on a high-fat diet were used to model atherosclerosis.
• RVS treatment effects on serum lipids, oxidative stress, and aortic tissue pathology were assessed.
• In vitro studies utilized human vascular smooth muscle cells (HVSMCs) challenged with oxidized LDL.
• The interaction between RVS, RCOR1, and C10ORF10 was investigated using molecular techniques.

Main Results:

• RVS significantly reduced total cholesterol, triglycerides, and LDL cholesterol in atherosclerotic mice.
• RVS treatment ameliorated oxidative stress, lipid deposition, plaque formation, and fibrosis in aortic tissues.
• In vitro, RVS decreased reactive oxygen species and suppressed HVSMC proliferation and migration.
• RVS upregulated REST corepressor 1 (RCOR1), which represses C10ORF10 transcription; RCOR1 silencing negated RVS benefits, while C10ORF10 silencing restored them.

Conclusions:

• Rosuvastatin alleviates atherosclerosis by enhancing RCOR1-mediated transcriptional repression of C10ORF10.
• This pathway effectively reduces oxidative stress and atherosclerotic plaque formation.
• The findings highlight a novel molecular mechanism for RVS in managing atherosclerosis.