Effects of Induction/Inhibition of Endogenous Heme Oxygenase-1 on Lipid Metabolism, Endothelial Function, and Atherosclerosis in Rabbits on a High Fat Diet
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- Liu Danan
- Department of Cardiology, The Affiliated Hospital of Guiyang Medical College, China
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- He Zuoyun
- Department of Cardiology, Xinqiao Hospital of The Third Military Medical University, China
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- Wu Lirong
- Department of Cardiology, The Affiliated Hospital of Guiyang Medical College, China
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- Fang Ying
- Department of Cardiology, The Affiliated Hospital of Guiyang Medical College, China
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Abstract
The heme oxygenase-1 (HO-1) / carbon monoxide (CO) system has been presumed as a therapeutic target for preventing atherosclerosis. However, the exact mechanism(s) underlying this system remains largely undefined. This study aims to examine the influence of induction/inhibition of HO-1 on atherosclerotic plaque using pharmacological approaches and to elucidate potential mechanisms. Rabbits were randomly assigned to receive a standard diet (control group), high fat diet (HFD), HFD plus HO inducer hemin (HFD + H group), and HFD plus an HO inhibitor, zinc protoporphyrin-9 (ZnPP9, HFD + Z group). Atherosclerotic plaque was evaluated using oil red O staining and histological analyses. Immunohistochemistry, western blotting, and RT-PCR were employed to study the expression of HO-1 and endothelin-1 (ET-1). Levels of CO, nitric oxide (NO), eNOS/iNOS activities, NF-κB activity, and TNF-α level were determined. No significant differences of serum lipid levels were observed among the HFD, HFD + Z, and HFD + H groups. In rabbits, HFD induced typical atherosclerotic plaque and increased intima/media thickness ratio, which was markedly reduced in the HFD + H group and further aggravated in the HFD + Z group. Furthermore, hemin increased HO-1 expression, CO levels, and eNOS activity, while decreasing iNOS levels, ET-1 expression, NF-κB activity, and TNF-α level. ZnPP9 caused opposite effects. Induction of the endogenous HO-1/CO system by hemin can prevent atherosclerosis though increasing CO levels, regulating eNOS activity, NF-κB activity, TNF-α levels, and ET-1 levels in rabbits. Our results add new evidence for the importance of HO-1 in the genesis and development of atherosclerosis and provide several possible mechanisms underlying the anti-atherosclerosis effects of HO-1.
Journal
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- Journal of Pharmacological Sciences
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Journal of Pharmacological Sciences 118 (1), 14-24, 2012
The Japanese Pharmacological Society
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Details 詳細情報について
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- CRID
- 1390001205181611776
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- NII Article ID
- 10030453991
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- NII Book ID
- AA11806667
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- COI
- 1:CAS:528:DC%2BC38Xhs1ygsLo%3D
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- ISSN
- 13478648
- 13478613
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- NDL BIB ID
- 023386130
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- PubMed
- 22261087
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- Text Lang
- en
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- Data Source
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- Abstract License Flag
- Disallowed