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HMG-CoA reductase i...
HMG-CoA reductase inhibitors regulate inflammatory transcription factors in human endothelial and vascular smooth muscle cells
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Dichtl, W (författare)
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Dulak, J (författare)
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Frick, M (författare)
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Alber, HF (författare)
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Schwarzacher, SP (författare)
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- Ares, Mikko (författare)
- Lund University,Lunds universitet,Kardiovaskulär forskning - immunitet och ateroskleros,Forskargrupper vid Lunds universitet,Cardiovascular Research - Immunity and Atherosclerosis,Lund University Research Groups
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- Nilsson, Jan (författare)
- Lund University,Lunds universitet,Kardiovaskulär forskning - immunitet och ateroskleros,Forskargrupper vid Lunds universitet,Cardiovascular Research - Immunity and Atherosclerosis,Lund University Research Groups
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Pachinger, O (författare)
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Weidinger, F (författare)
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(creator_code:org_t)
- 2003
- 2003
- Engelska.
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Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - 1524-4636. ; 23:1, s. 58-63
- Relaterad länk:
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http://dx.doi.org/10... (free)
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Objective-Pleiotropic atheroprotective effects of HMG-CoA reductase inhibitors may be mediated on the level of vascular gene transcription. The aim of this study was to characterize the effects of statins on the activation of transcription factors known to regulate inflammation and cell proliferation/differentiation. Methods and Results-Simvastatin, atorvastatin, and lovastatin (0.1 to 10 mumol/L) inhibited the binding of nuclear proteins to both the nuclear factor-kappa B (NF-kappaB) and activator protein-1 (AP-1) DNA consensus oligonucleotides in human endothelial and vascular smooth muscle cells as assessed by electrophoretic mobility shift assay (EMSA). The inhibitory effects of statins on NF-kappaB or AP-1-dependent transcriptional activity were examined by transient transfection studies. HMG-CoA reductase inhibitors upregulated IkappaB-alpha protein levels in endothelial cells and decreased c-Jun mRNA expression in smooth muscle cells as analyzed by Western and Northern blotting, respectively. Furthermore, statins inhibited DNA binding of hypoxia-inducible factor-1alpha. Downstream effects of statins included inhibition of plasminogen activator inhibitor-1 and vascular endothelial growth factor-A mRNA levels in endothelial cells. Conclusions-HMG-CoA reductase inhibitors downregulate the activation of transcription factors NF-kappaB, AP-1, and hypoxia-inducible factor-1alpha. These, findings support the concept that statins have antiinflammatory and antiproliferative effects that are relevant in the treatment of atherosclerotic diseases.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kardiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)
Nyckelord
- activator protein-1
- hypoxia-inducible
- vascular endothelial growth factor
- factor-1 alpha
- statins
- nuclear factor-kappa B
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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