| Humanin preserves endothelial function and prevents atherosclerotic plaque progression in hypercholesterolemic ApoE deficient mice. | |
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MedLine Citation:
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PMID: 21763658 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVE: Humanin (HN) is a cytoprotective peptide derived from endogenous mitochondria, expressed in the endothelial layer of human vessels, but its role in atherogenesis in vivo is not known. In vitro study, however, HN reduced oxidized low-density lipoprotein induced formation of reactive oxygen species and apoptosis. The present study tested the hypothesis that long term treatment with HN will have a protective role against endothelial dysfunction and progression of atherosclerosis in vivo. METHODS AND RESULTS: Daily intraperitonial injection of the HN analogue HNGF6A for 16 weeks prevented endothelial dysfunction and decreased atherosclerotic plaque size in the proximal aorta of ApoE-deficient mice fed on a high cholesterol diet, without showing direct vasoactive effects or cholesterol-reducing effects. HN was expressed in the endothelial layer on the aortic plaques. HNGF6A treatment reduced apoptosis and nitrotyrosine immunoreactivity in the aortic plaques without affecting the systemic cytokine profile. HNGF6A also preserved expression of endothelial nitric oxide synthase in aorta. CONCLUSIONS: HN may have a protective effect on endothelial function and progression of atherosclerosis by modulating oxidative stress and apoptosis in the developing plaque. |
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Authors:
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Yun K Oh; Adi R Bachar; David G Zacharias; Sung Gyun Kim; Junxiang Wan; Laura J Cobb; Lilach O Lerman; Pinchas Cohen; Amir Lerman |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2011-06-25 |
Journal Detail:
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Title: Atherosclerosis Volume: 219 ISSN: 1879-1484 ISO Abbreviation: Atherosclerosis Publication Date: 2011 Nov |
Date Detail:
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Created Date: 2011-11-01 Completed Date: 2012-02-27 Revised Date: 2012-05-30 |
Medline Journal Info:
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Nlm Unique ID: 0242543 Medline TA: Atherosclerosis Country: Ireland |
Other Details:
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Languages: eng Pagination: 65-73 Citation Subset: IM |
Copyright Information:
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Copyright © 2011 Elsevier Ireland Ltd. All rights reserved. |
Affiliation:
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Department of Internal Medicine, Divisions of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, United States. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Apolipoproteins E / deficiency Atherosclerosis / prevention & control Cholesterol, Dietary / administration & dosage Disease Progression Female Hypercholesterolemia / physiopathology* Intracellular Signaling Peptides and Proteins / pharmacology* Mice Plaque, Atherosclerotic / prevention & control* |
| Grant Support | |
ID/Acronym/Agency:
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AG 31750/AG/NIA NIH HHS; DK73608/DK/NIDDK NIH HHS; HL085307/HL/NHLBI NIH HHS; HL77131/HL/NHLBI NIH HHS; HL92954/HL/NHLBI NIH HHS; P30DK063491/DK/NIDDK NIH HHS; R01 AG034430/AG/NIA NIH HHS; R01AG034430/AG/NIA NIH HHS; R01GM090311/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Apolipoproteins E; 0/Cholesterol, Dietary; 0/Intracellular Signaling Peptides and Proteins; 0/humanin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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