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Critical Promoter Region for Statin-Induced Human Endothelial Nitric Oxide Synthase (eNOS) Transcription in EA.hy926 Cells
- Source :
- Journal of Atherosclerosis and Thrombosis. 20:321-329
- Publication Year :
- 2013
- Publisher :
- Japan Atherosclerosis Society, 2013.
-
Abstract
- Aim Statins have many anti-atherogenic effects apart from reducing the serum level of low density lipoprotein cholesterol (LDL-C). For instance, statins can enhance the expression of endothelial nitric oxide synthase (eNOS), at least partly by upregulating its transcription. Although it has been reported that -786 T/C polymorphism of the promoter region has an important influence on statininduced transcription of the human eNOS gene, much remains unclear about statin-induced eNOS transcription. We tried to identify other statin-responsive promoter regions. Methods A human endothelial cell line (EA.hy926 cells) was treated with pitavastatin, atorvastatin, or fluvastatin, after which eNOS mRNA levels were assessed by quantitative real-time RT-PCR. EA.hy926 cells were also transiently transfected with luciferase reporter genes driven by various lengths of the human eNOS promoter and were treated with statins before luciferase activity was measured. Results Statin treatment increased eNOS mRNA levels in EA.hy926 cells. In addition, cells transfected with the reporter gene driven by the eNOS promoter fragment starting from position -740 exhibited a pitavastatin-induced increase of luciferase activity, which was not observed in cells transfected with the reporter gene driven by the fragment starting from -727. Similar results were also obtained with atorvastatin and fluvastatin. Conclusions Statins enhanced eNOS expression in EA.hy926 cells, at least partly by inducing its transcription. Although a statin-responsive sequence that could function even in a heterologous promoter was not precisely identified, the region of the human eNOS promoter around position -730 seems to be critical for statin-induced transcriptional activation.
- Subjects :
- Indoles
Nitric Oxide Synthase Type III
Transcription, Genetic
Fatty Acids, Monounsaturated
Genes, Reporter
Enos
Atorvastatin
Internal Medicine
medicine
Humans
Pyrroles
Luciferase
RNA, Messenger
Fluvastatin
Promoter Regions, Genetic
Pitavastatin
Cells, Cultured
Reporter gene
biology
Chemistry
Biochemistry (medical)
Promoter
Transfection
biology.organism_classification
Molecular biology
Endothelial stem cell
Heptanoic Acids
Quinolines
lipids (amino acids, peptides, and proteins)
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Cardiology and Cardiovascular Medicine
Plasmids
medicine.drug
Subjects
Details
- ISSN :
- 18803873 and 13403478
- Volume :
- 20
- Database :
- OpenAIRE
- Journal :
- Journal of Atherosclerosis and Thrombosis
- Accession number :
- edsair.doi.dedup.....f68476870d615586cebc1f4d0e72e0fa