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

Research output: Contribution to journalArticle

33 Citations (Scopus)

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

Fingerprint

Fibroblast Growth Factor 2
Epigenomics
Aspirin
Coronary Vessels
Endothelial Cells
Myocardial Infarction
Methylation
LDL Lipoproteins
Apoptosis
Survival
oxidized low density lipoprotein
Chest Pain
Therapeutics

Keywords

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

ASJC Scopus subject areas

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

Cite this

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

In: Cardiovascular Research, Vol. 99, No. 1, 01.07.2013, p. 137-145.

Research output: Contribution to journalArticle

Chang, Po Yuan ; Chen, Yi Jie ; Chang, Fu Hsiung ; Lu, Jonathan ; Huang, Wen Huei ; Yang, Tzu Ching ; Lee, Yuan Teh ; Chang, Shwu Fen ; Lu, Shao Chun ; Chen, Chu Huang. / 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. In: Cardiovascular Research. 2013 ; Vol. 99, No. 1. pp. 137-145.
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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.",
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T1 - Aspirin protects human coronary artery endothelial cells against atherogenic electronegative LDL via an epigenetic mechanism

T2 - A novel cytoprotective role of aspirin in acute myocardial infarction

AU - Chang, Po Yuan

AU - Chen, Yi Jie

AU - Chang, Fu Hsiung

AU - Lu, Jonathan

AU - Huang, Wen Huei

AU - Yang, Tzu Ching

AU - Lee, Yuan Teh

AU - Chang, Shwu Fen

AU - Lu, Shao Chun

AU - Chen, Chu Huang

PY - 2013/7/1

Y1 - 2013/7/1

N2 - 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.

AB - 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.

KW - Aspirin

KW - DNA methylation

KW - Genes

KW - Lipoproteins

KW - Myocardial infarction

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