Apolipoprotein A-I and A-I mimetic peptides: a role in atherosclerosis.
Apolipoprotein A-I and A-I mimetic peptides: a role in atherosclerosis.
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DOI：
10.2147/jir.s12983
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发表时间：
2011
影响因子：
4.5
通讯作者：
Reardon CA
中科院分区：
文献类型：
--
作者：
Getz GS;Reardon CA
心血管疾病仍然是西方世界发病率和死亡率的主要原因。动脉粥样硬化是大多数心血管疾病的根本原因。动脉粥样硬化是一种缓慢演变的慢性炎症性疾病，涉及大中型动脉内膜，是由于高血脂水平（尤其是低密度脂蛋白）而引发的。先天免疫和适应性免疫的细胞都参与了这种慢性炎症。尽管高血浆LDL水平是动脉粥样硬化发展的大多数阶段的主要贡献者，但HDL及其主要蛋白apoA-I具有减弱甚至可能逆转动脉粥样硬化的性质。两个主要功能是诱导胆固醇从动脉壁中的细胞（特别是脂质负载的巨噬细胞）流出以转移到肝脏的能力，这一过程被称为胆固醇逆向转运，以及减弱LDL的促炎性质的能力。从负载脂质的巨噬细胞中去除细胞胆固醇也可以是抗炎的。apoA-I模拟肽是增强HDL抗动脉粥样硬化、抗炎特性的最有希望的疗法之一。这些肽中的几种已显示出促进细胞胆固醇流出，减弱巨噬细胞产生促炎细胞因子，并减弱LDL的促炎特性。后一种效应可能与它们对LDL中存在的氧化脂质的高亲和力有关。这篇综述讨论了肽的功能特性及其对实验性动脉粥样硬化的影响和人类初步临床研究的结果。
Cardiovascular disease remains a major cause of morbidity and mortality in the westernized world. Atherosclerosis is the underlying cause of most cardiovascular diseases. Atherosclerosis is a slowly evolving chronic inflammatory disorder involving the intima of large and medium sized arteries that is initiated in response to high plasma lipid levels, especially LDL. Cells of both the innate and adaptive immunity are involved in this chronic inflammation. Although high plasma LDL levels are a major contributor to most stages of the evolution of atherosclerosis, HDL and its major protein apoA-I possess properties that attenuate and may even reverse atherosclerosis. Two major functions are the ability to induce the efflux of cholesterol from cells, particularly lipid-loaded macrophages, in the artery wall for transfer to the liver, a process referred to as reverse cholesterol transport, and the ability to attenuate the pro-inflammatory properties of LDL. The removal of cellular cholesterol from lipid-loaded macrophages may also be anti-inflammatory. One of the most promising therapies to enhance the anti-atherogenic, anti-inflammatory properties of HDL is apoA-I mimetic peptides. Several of these peptides have been shown to promote cellular cholesterol efflux, attenuate the production of pro-inflammatory cytokines by macrophages, and to attenuate the pro-inflammatory properties of LDL. This latter effect may be related to their high affinity for oxidized lipids present in LDL. This review discusses the functional properties of the peptides and their effect on experimental atherosclerosis and the results of initial clinical studies in humans.