Aspirin protects human coronary artery endothelial cells against atherogenic electronegative LDL via an epigenetic mechanism: A novel cytoprotective role of aspirin in acute myocardial infarction

Po Yuan Chang, Yi Jie Chen, Fu Hsiung Chang, Jonathan Lu, Wen Huei Huang, Tzu Ching Yang, Yuan Teh Lee, Shwu Fen Chang, Shao Chun Lu, Chu Huang Chen

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Abstract

AimsL5 is the most negatively charged subfraction of human low-density lipoprotein (LDL) and is the only subfraction of LDL capable of inducing apoptosis in cultured vascular endothelial cells (ECs) by inhibiting fibroblast growth factor-2 (FGF2) transcription. We examined whether plasma L5 levels are elevated in patients with ST-segment elevation myocardial infarction (STEMI) and whether aspirin provides epigenetic protection of human coronary artery ECs (HCAECs) exposed to L5.Methods and resultsPlasma L5 levels were compared between patients with STEMI (n = 10) and control subjects with chest pain syndrome but a normal coronary arteriogram (n = 5). L5 was isolated from the plasma of STEMI patients and control subjects, and apoptosis, FGF2 expression, and FGF2 promoter methylation were examined in HCAECs treated with L5 and aspirin. Plasma L5 levels were significantly higher in STEMI patients than in control subjects (P <0.001). Treatment of HCAECs with L5 resulted in reduced survival and FGF2 expression and increased CpG methylation of the FGF2 promoter. Co-treatment of HCAECs with L5 and a physiologically relevant, low concentration of aspirin (0.2 mM) attenuated the adverse effects of L5 on HCAEC survival, FGF2 expression, and FGF2 promoter methylation. In contrast, high concentrations of aspirin (≥1.0 mM) accentuated the effects of L5.ConclusionsOur results show that L5 levels are significantly increased in STEMI patients. Furthermore, L5 impairs HCAEC function through CpG methylation of the FGF2 promoter, which is suppressed in the presence of low-concentration aspirin. Our results provide evidence of a novel mechanism of aspirin in the prevention of MI.

Original languageEnglish
Pages (from-to)137-145
Number of pages9
JournalCardiovascular Research
Volume99
Issue number1
DOIs
Publication statusPublished - Jul 1 2013

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Keywords

  • Aspirin
  • DNA methylation
  • Genes
  • Lipoproteins
  • Myocardial infarction

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)
  • Physiology

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