An apolipoprotein A-I mimetic peptide designed with a reductionist approach stimulates reverse cholesterol transport and reduces atherosclerosis in mice.
An apolipoprotein A-I mimetic peptide designed with a reductionist approach stimulates reverse cholesterol transport and reduces atherosclerosis in mice.
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DOI：
10.1371/journal.pone.0068802
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Sviridov D
中科院分区：
文献类型：
--
作者：
Ditiatkovski M;D'Souza W;Kesani R;Chin-Dusting J;de Haan JB;Remaley A;Sviridov D
载脂蛋白A - I（apoA - I）模拟肽被认为是一种有前景的预防和/或治疗动脉粥样硬化的新型治疗方法。一种载脂蛋白A - I模拟肽ELK - 2A2K2E是通过简化方法设计的，它在促进胆固醇外流方面表现出非凡的活性，但在体外的抗炎和抗氧化特性一般。在这项研究中，我们将这些体外特性与该肽在小鼠模型中改变胆固醇逆向转运速率和动脉粥样硬化发展的能力进行了比较。该肽提高了C57BL / 6小鼠的胆固醇逆向转运速率，并减少了接受高脂肪饮食的Apoe - / - 小鼠的动脉粥样硬化。该肽略微减小了主动脉弓斑块的大小，但在减轻血管炎症和氧化方面非常有效。给接受高脂肪饮食的Apoe - / -小鼠施用该肽降低了总胆固醇、高密度脂蛋白胆固醇、非高密度脂蛋白胆固醇和甘油三酯的水平。它以较大的高密度脂蛋白颗粒为代价增加了血浆中小高密度脂蛋白颗粒的比例，并提高了血浆促进胆固醇外流的能力。因此，ELK - 2A2K2E肽减少了Apoe - / -小鼠的动脉粥样硬化，然而，慢性体内给药后的功能活性特征与急性体外研究中发现的不同。
Apolipoprotein A-I (apoA-I) mimetic peptides are considered a promising novel therapeutic approach to prevent and/or treat atherosclerosis. An apoA-I mimetic peptide ELK-2A2K2E was designed with a reductionist approach and has shown exceptional activity in supporting cholesterol efflux but modest anti-inflammatory and anti-oxidant properties in vitro. In this study we compared these in vitro properties with the capacity of this peptide to modify rates of reverse cholesterol transport and development of atherosclerosis in mouse models. The peptide enhanced the rate of reverse cholesterol transport in C57BL/6 mice and reduced atherosclerosis in Apoe−/− mice receiving a high fat diet. The peptide modestly reduced the size of the plaques in aortic arch, but was highly active in reducing vascular inflammation and oxidation. Administration of the peptide to Apoe−/− mice on a high fat diet reduced the levels of total, high density lipoprotein and non-high density lipoprotein cholesterol and triglycerides. It increased the proportion of smaller HDL particles in plasma at the expense of larger HDL particles, and increased the capacity of the plasma to support cholesterol efflux. Thus, ELK-2A2K2E peptide reduced atherosclerosis in Apoe−/− mice, however, the functional activity profile after chronic in vivo administration was different from that found in acute in vitro studies.
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DOI：
10.1253/circj.cj-11-0460
发表时间：
2011
期刊：
Circulation journal : official journal of the Japanese Circulation Society
影响因子：
--
作者：
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6.5
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DOI：
10.1124/jpet.110.167890
发表时间：
2010-08-10
影响因子：
3.5
作者：
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DOI：
10.1177/1074248411434598
发表时间：
2012-09-01
影响因子：
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作者：
Qin, Shucun;Kamanna, Vaijinath S.;Kashyap, Moti L.
通讯作者：
Kashyap, Moti L.
影响因子：
37.8
作者：
Navab, M;Anantharamaiah, GM;Fogelman, AM
通讯作者：
Fogelman, AM