| Heme oxygenase-1 inhibits progression and destabilization of vulnerable plaques in a rabbit model of atherosclerosis. | |
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MedLine Citation:
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PMID: 22004613 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Although heme oxygenase-1 (HO-1) has been implicated in protection against atherogenesis, its role in vulnerable plaques remains to be fully elucidated. This study was aimed to explore the effect of HO-1 on the progression and stabilization of vulnerable plaques and the possible mechanism. We established a vulnerable plaque model by local transfection with recombinant p53 adenovirus to plaques in rabbits fed a high-cholesterol diet. HO-1 activity was modulated by intraperitoneal injection of hemin or Sn-protoporphyrin IX (SnPP). HO-1 induction by hemin inhibited the progression of atherosclerotic lesions and changed the plaque morphology and composition into a more stable phenotype. In addition, hemin treatment is associated with a reduction in matrix metalloproteinase-9, interleukin-6 and tumor necrosis factor-α production, an increase in interleukin-10 level, as well as a decrease of TUNEL labeled apoptosis of smooth muscle cells in lesions. Compared with the control group, aortic nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) activity decreased markedly, whereas endothelial nitric oxide synthase (eNOS) activity increased significantly in the Hemin group. In contrast, inhibition of HO-1 by SnPP induced reversed effects and augmented plaque progression and vulnerability. After pharmacological triggering, the incidence of plaque disruption in SnPP group was significantly higher than that in control group (79% vs. 33%, P<0.05), while no plaque in hemin group developed disruption (0% vs. 33%, P<0.05). These findings suggest that HO-1 induction could delay progression and enhance stability of atherosclerotic plaques, possibly through the attenuation of plaque inflammation and apoptosis, and the suppression of iNOS/NO production. |
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Authors:
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Tingting Li; Hongbo Tian; Yuxia Zhao; Fengshuang An; Lei Zhang; Jianning Zhang; Jie Peng; Yun Zhang; Yuan Guo |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-10-10 |
Journal Detail:
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Title: European journal of pharmacology Volume: - ISSN: 1879-0712 ISO Abbreviation: - Publication Date: 2011 Oct |
Date Detail:
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Created Date: 2011-10-18 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 1254354 Medline TA: Eur J Pharmacol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011. Published by Elsevier B.V. |
Affiliation:
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The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University Qilu Hospital, Jinan, Shandong 250012, PR China. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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