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Atorvastatin Can Modulate DNA Damage Repair in Endothelial Cells Exposed to Mitomycin C

Maxim Sinitsky1, Maxim Asanov1, Anna Sinitskaya1

  • 1Laboratory of Genome Medicine, Research Institute for Complex Issues of Cardiovascular Diseases, Kemerovo 650002, Russia.

International Journal of Molecular Sciences
|April 13, 2023
PubMed

Insights

Atorvastatin modulates DNA repair in human endothelial cells differently based on treatment timing and cell type. This finding is crucial for understanding statin side effects and treating atherosclerosis patients with high genotoxic load.

Area of Science:

  • Cardiovascular Biology
  • Molecular Biology
  • Genetics

Background:

  • HMG-CoA reductase inhibitors (statins) are key in atherosclerosis therapy.
  • Statins exhibit pleiotropic effects, including DNA repair regulation.
  • Understanding these effects is vital for patient treatment.

Purpose of the Study:

  • To investigate the impact of atorvastatin on DNA damage and repair gene expression in human endothelial cells exposed to mitomycin C.
  • To determine if atorvastatin's effects are dependent on cell type and incubation strategy.

Main Methods:

  • Human coronary artery endothelial cells (HCAEC) and internal thoracic artery endothelial cells (HITAEC) were exposed to mitomycin C (MMC) with or without atorvastatin (Atv).
  • Cytogenetic damage (micronuclei, nucleoplasmic bridges, nuclear buds) and DNA repair gene expression (DDB1, ERCC4, ERCC5) were analyzed.
  • Different incubation schemes (co-treatment vs. sequential treatment) were employed.

Main Results:

  • Atorvastatin modulated DNA damage markers (micronuclei, nucleoplasmic bridges) in a cell- and incubation-dependent manner.
  • Expression of DNA repair genes (DDB1, ERCC4, ERCC5) varied significantly between treatment groups and cell types.
  • Specific gene expression patterns (e.g., DDB1 downregulation, ERCC5 upregulation) were observed under different atorvastatin treatment conditions.

Conclusions:

  • Atorvastatin's modulation of DNA damage repair in endothelial cells is complex and context-specific.
  • Findings highlight the importance of considering incubation schemes and cell types in statin therapy.
  • This research contributes to understanding statin's pleiotropic actions and optimizing atherosclerosis treatment in genotoxic conditions.
Keywords:
DNA damageatorvastatincytogeneticsgene expressiongenotoxic stressmicronucleus assay

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