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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.
MedLine Citation:
PMID:  23519265     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
AIMS: L5 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. Cotreatment of HCAECs with L5 and a physiologically relevant, low concentration of aspirin (0.2&emsp14;mM) attenuated the adverse effects of L5 on HCAEC survival, FGF2 expression, and FGF2 promoter methylation. In contrast, high concentrations of aspirin (≥ 1.0&emsp14;mM) accentuated the effects of L5. CONCLUSIONS: Our 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.
Authors:
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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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-3-20
Journal Detail:
Title:  Cardiovascular research     Volume:  -     ISSN:  1755-3245     ISO Abbreviation:  Cardiovasc. Res.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-3-22     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0077427     Medline TA:  Cardiovasc Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Departments of Internal Medicine.
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