| Apolipoprotein A-I mimetic peptides: a potential new therapy for the prevention of atherosclerosis. | |
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MedLine Citation:
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PMID: 20395699 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The beneficial effects of high-density lipoprotein (HDL) on atherosclerosis have largely been attributed to its major protein, apolipoprotein A-I (apoA-I). Used as a therapeutic intervention, apoA-I is a large protein that requires venous administration, and is both difficult and expensive to manufacture. Because of these problems with apoA-I, the generation of smaller, easier to manufacture apoA-I mimetic peptides has become a target for pharmacologic development in the therapeutic management of human atherosclerosis. A potent apoA-I mimetic peptide, 4F, was found to have significant activity in various inflammatory states in both mice and monkeys. The anti-inflammatory and antiatherogenic effects of 4F include increased pre-beta HDL formation, increased cholesterol efflux, the conversion of pro-inflammatory HDL to anti-inflammatory HDL, and reduced lipoprotein oxidation. In addition, improved arterial vasoreactivity is another important function of 4F. In a rat model of diabetes, D-4F increased arterial concentrations of heme oxygenase-1 (HO-1) and superoxide dismutase, decreased superoxide levels, reduced levels of circulating endothelial cells, decreased endothelial cell fragmentation, and restored arterial vasoreactivity to normal. In a mouse model of systemic sclerosis, D-4F functioned to improve vasodilation and angiogenic potential, while reducing myocardial inflammation and oxidative stress. With respect to mouse models of heart transplant-associated atherosclerosis, D-4F induced HO-1. In addition, D-4F was shown to improve cognitive performance in low-density lipoprotein-receptor null mice with Western diet-induced cognitive decline. D-4F also reduced the kidney content of oxidized phospholipids in a mouse model of hyperlipidemia-induced renal inflammation. In early human studies in patients with significant cardiovascular risk, a single dose of oral D-4F was found to safely improve the anti-inflammatory index of HDL. L-4F is also being studied in clinical trials as a potential treatment modality for obesity and the metabolic syndrome. |
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Authors:
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Courtney B Sherman; Stephen J Peterson; William H Frishman |
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Publication Detail:
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Type: Journal Article; Review |
Journal Detail:
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Title: Cardiology in review Volume: 18 ISSN: 1538-4683 ISO Abbreviation: Cardiol Rev Publication Date: 2010 May-Jun |
Date Detail:
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Created Date: 2010-04-16 Completed Date: 2010-07-13 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9304686 Medline TA: Cardiol Rev Country: United States |
Other Details:
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Languages: eng Pagination: 141-7 Citation Subset: IM |
Affiliation:
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Department of Medicine, University of California, San Francisco, CA, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Apolipoprotein A-I / therapeutic use* Atherosclerosis / metabolism, prevention & control* Biomimetic Materials / therapeutic use* Disease Models, Animal Humans Lipoproteins, HDL / metabolism Mice Peptides / therapeutic use Rats |
| Chemical | |
Reg. No./Substance:
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0/Apolipoprotein A-I; 0/D-4F peptide; 0/L-4F peptide; 0/Lipoproteins, HDL; 0/Peptides |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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