Document Detail


Expression of apolipoprotein A-I in rabbit carotid endothelium protects against atherosclerosis.
MedLine Citation:
PMID:  21772254     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Expression of atheroprotective genes in the blood vessel wall is potentially an effective means of preventing or reversing atherosclerosis. Development of this approach has been hampered by lack of a suitable gene-transfer vector. We used a helper-dependent adenoviral (HDAd) vector to test whether expression of apolipoprotein A-I (apoA-I) in the artery wall could retard the development of atherosclerosis in hyperlipidemic rabbits. Carotid arteries were infused with an HDAd expressing rabbit apoA-I or a "null" HDAd and harvested 2 and 4 weeks later. ApoA-I mRNA and protein were detected only in HDAdApoAI arteries. Lesion size, lipid and macrophage content, and adhesion molecule expression were similar in both groups at 2 weeks. Between 2 and 4 weeks, most of these measures of atherosclerosis increased in HDAdNull arteries, but were stable or decreased in HDAdApoAI arteries (P ≤ 0.04 for all end points in 4-week HDAdApoAI versus HDAdNull arteries). A longer-term study in chow-fed rabbits revealed persistence of HDAd vector DNA and apoA-I expression for ≥48 weeks, with stable vector DNA content and apoA-I expression from 4 to 48 weeks. Expression of apoA-I in arterial endothelium significantly retards atherosclerosis. HDAd provides prolonged, stable expression of a therapeutic transgene in the artery wall.
Authors:
Rowan Flynn; Kun Qian; Chongren Tang; Nagadhara Dronadula; Joshua M Buckler; Bo Jiang; Shan Wen; Helén L Dichek; David A Dichek
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-07-19
Journal Detail:
Title:  Molecular therapy : the journal of the American Society of Gene Therapy     Volume:  19     ISSN:  1525-0024     ISO Abbreviation:  Mol. Ther.     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-10-03     Completed Date:  2012-02-03     Revised Date:  2014-09-24    
Medline Journal Info:
Nlm Unique ID:  100890581     Medline TA:  Mol Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1833-41     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Apolipoprotein A-I / genetics,  metabolism*
Atherosclerosis / prevention & control*
Carotid Arteries / metabolism*
Cholesterol / metabolism
Endothelium, Vascular / metabolism*
Macrophages / metabolism
Mice
Mice, Knockout
RNA, Messenger / genetics
Rabbits
Tunica Intima / metabolism,  pathology
Grant Support
ID/Acronym/Agency:
HL076226/HL/NHLBI NIH HHS; P30DK017047/DK/NIDDK NIH HHS; R01 HL076226/HL/NHLBI NIH HHS; T32 HL007828/HL/NHLBI NIH HHS; T32HL007828/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Apolipoprotein A-I; 0/RNA, Messenger; 97C5T2UQ7J/Cholesterol
Comments/Corrections

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