| 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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MedLine Citation:
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PMID: 22261087 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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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. |
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Authors:
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Danan Liu; Zuoyun He; Lirong Wu; Ying Fang |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Journal of pharmacological sciences Volume: 118 ISSN: 1347-8648 ISO Abbreviation: J. Pharmacol. Sci. Publication Date: 2012 |
Date Detail:
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Created Date: 2012-01-20 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101167001 Medline TA: J Pharmacol Sci Country: Japan |
Other Details:
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Languages: eng Pagination: 14-24 Citation Subset: IM |
Affiliation:
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Department of Cardiology, The Affiliated Hospital of Guiyang Medical College, China. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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