| Antiatherogenic effects of newly developed apolipoprotein A-I mimetic peptide/phospholipid complexes against aortic plaque burden in Watanabe-heritable hyperlipidemic rabbits. | |
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MedLine Citation:
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PMID: 21696737 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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This study analyzed the antiatherogenic effects of newly developed apolipoprotein A-I (ApoA-I) mimetic peptide/phospholipid complexes (ETC-642) against the aortic plaque burden in vivo. We used human macrophage cells to analyze cholesterol efflux by ETC-642. Watanabe-heritable hyperlipidemic (WHHL) rabbits were divided into 3 groups: low- (15mg/kg) and high-dose ETC-642 (50mg/kg), and placebo. The test material was injected twice/week for 12 weeks. The aortic plaque burden was assessed by intravascular ultrasound (IVUS) at 0 and 12 weeks. Plasma lipid profiles were analyzed by capillary isotachophoresis every 4 weeks. ETC-642 had an effect on cholesterol efflux comparable to that of conventional rHDL. In WHHL rabbits, high-dose ETC-642 inhibited the progression of aortic atherosclerosis compared to placebo. There was no change in the percentage of plaque volume (%PV) in the high-dose group between before (30.9%) and after infusion (28.6%), whereas there was a significant increase in the control group from 27.8% to 37.9%. ETC-642 significantly reduced charge-modified low-density lipoprotein (LDL) by converting more negative-charged modified LDL to less negative-charged LDL, and reduced small dense (sd) LDL by converting it into large, buoyant (lb) LDL. Changes in the %PV were positively correlated with changes in negative-charged modified LDL (r=0.61, p<0.01) and sdLDL (r=0.59, p<0.01), and negatively correlated with changes in less negative-charged LDL (r=-0.43, p<0.01) and lbLDL (r=-0.57, p<0.01). In conclusion, the ETC-642-induced remodeling of sdLDL to large and lbLDL and the enhancement of cholesterol efflux may prevent progression of the aortic plaque burden. HDL-based therapy may be useful for preventing the progression of plaque volume. |
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Authors:
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Atsushi Iwata; Shin-Ichiro Miura; Bo Zhang; Satoshi Imaizumi; Yoshinari Uehara; Masashi Shiomi; Keijiro Saku |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-6-1 |
Journal Detail:
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Title: Atherosclerosis Volume: - ISSN: 1879-1484 ISO Abbreviation: - Publication Date: 2011 Jun |
Date Detail:
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Created Date: 2011-6-23 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0242543 Medline TA: Atherosclerosis Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011 Elsevier Ireland Ltd. All rights reserved. |
Affiliation:
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Department of Cardiology, Fukuoka University School of Medicine, 7-45-1 Nanakuma, Jonan-Ku, Fukuoka 814-0180, Japan. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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