HDL apolipoprotein-related peptides in the treatment of atherosclerosis and other inflammatory disorders.
HDL apolipoprotein-related peptides in the treatment of atherosclerosis and other inflammatory disorders.
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DOI：
10.2174/138161210793292492
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发表时间：
2010
影响因子：
3.1
通讯作者：
Reardon CA
中科院分区：
文献类型：
--
作者：
Getz GS;Wool GD;Reardon CA
正在评估升高高密度脂蛋白水平或改变高密度脂蛋白的炎症特性是否可能治疗动脉粥样硬化，动脉粥样硬化是大多数心血管疾病的潜在机制。一个有前途的方法是使用小HDL载脂蛋白相关的模拟肽。许多模拟apoA-I（HDL中的主要载脂蛋白）中重复的两亲性α-螺旋结构的肽已在体外和动物模型中进行了检测。几种肽已被证明可以减少早期动脉粥样硬化病变，但不能减少更成熟的病变，除非与他汀类药物联合给药。这些肽还影响血管壁的血管生物学，并防止其他急性和慢性炎症性疾病。生物活性肽能够降低LDL和HDL的促炎特性，这可能是由于它们对氧化脂质的高亲和力。它们还能够影响其他过程，包括ABCA 1介导的巨噬细胞中JAK-2的活化，这可能有助于它们的抗动脉粥样硬化功能。最初的研究涉及单体18个氨基酸的肽，但串联肽正在研究其抗动脉粥样硬化和抗炎特性，因为它们更接近apoA-I的重复结构。也已经研究了基于其他HDL相关蛋白如apoE、apoJ和SAA的肽。它们的作用机制似乎与基于apoA-I的模拟物不同。
Elevations of HDL levels or modifying the inflammatory properties of HDL are being evaluated as possible treatment of atherosclerosis, the underlying mechanism responsible for most cardiovascular diseases. A promising approach is the use of small HDL apoprotein-related mimetic peptides. A number of peptides mimicking the repeating amphipathic α-helical structure in apoA-I, the major apoprotein in HDL, have been examined in vitro and in animal models. Several peptides have been shown to reduce early atherosclerotic lesions, but not more mature lesions unless coadminstered with statins. These peptides also influence the vascular biology of the vessel wall and protect against other acute and chronic inflammatory diseases. The biologically active peptides are capable of reducing the pro-inflammatory properties of LDL and HDL, likely due to their high affinity for oxidized lipids. They are also capable of influencing other processes, including ABCA1 mediated activation of JAK-2 in macrophages, which may contribute to their anti-atherogenic function. The initial studies involved monomeric 18 amino acid peptides, but tandem peptides are being investigated for their anti-atherogenic and anti-inflammatory properties as they more closely resemble the repeating structure of apoA-I. Peptides based on other HDL associated proteins such as apoE, apoJ and SAA have also been studied. Their mechanism of action appears to be distinct from the apoA-I based mimetics.