Document Detail


Humanin preserves endothelial function and prevents atherosclerotic plaque progression in hypercholesterolemic ApoE deficient mice.
MedLine Citation:
PMID:  21763658     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-06-25
Journal Detail:
Title:  Atherosclerosis     Volume:  219     ISSN:  1879-1484     ISO Abbreviation:  Atherosclerosis     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-11-01     Completed Date:  2012-02-27     Revised Date:  2014-09-10    
Medline Journal Info:
Nlm Unique ID:  0242543     Medline TA:  Atherosclerosis     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  65-73     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
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:
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 AG031750/AG/NIA NIH HHS; R01AG034430/AG/NIA NIH HHS; R01GM090311/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Apolipoproteins E; 0/Cholesterol, Dietary; 0/Intracellular Signaling Peptides and Proteins; 0/humanin
Comments/Corrections

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