| 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. | |
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MedLine Citation:
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PMID: 19701094 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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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. |
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Authors:
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Giovanni Cimmino; Wei Chen; Walter S Speidl; Chiara Giannarelli; Borja Ibanez; Valentin Fuster; Roger Hajjar; Christopher E Walsh; Juan J Badimon |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of cardiovascular pharmacology Volume: 54 ISSN: 1533-4023 ISO Abbreviation: J. Cardiovasc. Pharmacol. Publication Date: 2009 Nov |
Date Detail:
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Created Date: 2009-12-08 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7902492 Medline TA: J Cardiovasc Pharmacol Country: United States |
Other Details:
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Languages: eng Pagination: 405-11 Citation Subset: IM |
Affiliation:
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Mount Sinai School of Medicine, New York, NY 10029, USA. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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