Source:http://linkedlifedata.com/resource/pubmed/id/19701094
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
5
|
| pubmed:dateCreated |
2009-12-8
|
| pubmed:abstractText |
High levels of high-density lipoprotein (HDL) have protective effects against atherosclerosis and cardiovascular diseases. The postulated mechanism of action for these benefits is an enhanced reverse cholesterol transport. Apolipoprotein A-I (ApoA-I) is the major protein of HDL. The clinical benefits of raising ApoA-I/HDL have been clearly established by clinical and epidemiological studies. Despite these observations, there are not very effective pharmacological means for raising HDL. ApoA-I gene delivery by viral vectors seems a promising strategy to raise ApoA-I/HDL levels. Sustained gene expression in animals and humans has been attained using adeno-associated viral (AAV) vectors. The aim of the present study was to determine the efficiency, safety, and biological activity of human ApoA-I intramuscularly delivered using an AAV vector in mice. AAV serotype 8 vectors encoding for human ApoA-I transgene were administered intraportally and intramuscularly in ApoA-I- deficient animals. ApoA-I levels were measured every 2 weeks post administration. The effectiveness of the generated HDL was tested in vitro in cholesterol-loaded macrophages. The administration of the vectors resulted in a significant and sustained increase in ApoA-I and HDL plasma levels for up to 16 weeks at similar extent by both routes of administration. Activity of the generated HDL in removal of cholesterol from cholesterol-loaded macrophages was similar in both groups. Our data suggest that intramuscular AAV8-mediated gene transfer of human ApoA-I results in a significant and maintained increase in ApoA-I and functional HDL.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Nov
|
| pubmed:issn |
1533-4023
|
| pubmed:author | |
| pubmed:issnType |
Electronic
|
| pubmed:volume |
54
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
405-11
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| pubmed:meshHeading |
pubmed-meshheading:19701094-Animals,
pubmed-meshheading:19701094-Apolipoprotein A-I,
pubmed-meshheading:19701094-Blotting, Western,
pubmed-meshheading:19701094-Cell Line,
pubmed-meshheading:19701094-Creatine Kinase,
pubmed-meshheading:19701094-Dependovirus,
pubmed-meshheading:19701094-Gene Expression,
pubmed-meshheading:19701094-Gene Transfer Techniques,
pubmed-meshheading:19701094-Genetic Vectors,
pubmed-meshheading:19701094-Humans,
pubmed-meshheading:19701094-Injections, Intramuscular,
pubmed-meshheading:19701094-Lipoproteins, HDL,
pubmed-meshheading:19701094-Lipoproteins, LDL,
pubmed-meshheading:19701094-Liver,
pubmed-meshheading:19701094-Macrophages,
pubmed-meshheading:19701094-Male,
pubmed-meshheading:19701094-Mice,
pubmed-meshheading:19701094-Mice, Knockout,
pubmed-meshheading:19701094-Muscle, Skeletal,
pubmed-meshheading:19701094-Oxidation-Reduction,
pubmed-meshheading:19701094-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:19701094-Transfection
|
| pubmed:year |
2009
|
| pubmed:articleTitle |
Safe and sustained overexpression of functional apolipoprotein A-I/high-density lipoprotein in apolipoprotein A-I-null mice by muscular adeno-associated viral serotype 8 vector gene transfer.
|
| pubmed:affiliation |
Mount Sinai School of Medicine, New York, NY 10029, USA.
|
| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|