Vasculoprotective Effects of Apolipoprotein Mimetic Peptides: An Evolving Paradigm In Hdl Therapy (Vascular Disease Prevention, In Press.).
Vasculoprotective Effects of Apolipoprotein Mimetic Peptides: An Evolving Paradigm In Hdl Therapy (Vascular Disease Prevention, In Press.).
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载脂蛋白模拟肽的血管保护作用：HDL疗法中不断发展的范例（预防血管疾病，印刷中）。
DOI：
10.2174/1567270000906010122
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发表时间：
2009-01-01
期刊：
影响因子：
--
通讯作者：
Anantharamaiah GM
中科院分区：
文献类型：
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作者：
White CR;Datta G;Mochon P;Zhang Z;Kelly O;Curcio C;Parks D;Palgunachari M;Handattu S;Gupta H;Garber DW;Anantharamaiah GM
高密度脂蛋白（HDL）及其主要蛋白组分载脂蛋白A-I（apoA-I）的抗动脉粥样硬化作用主要被认为是由于它们介导胆固醇逆向转运的能力。这些药物还具有防止低密度脂蛋白（LDL）氧化修饰的抗氧化特性和包括抑制内皮细胞粘附分子表达的抗炎特性。Fracket研究的结果显示，HDL水平的降低是冠状动脉疾病（CAD）的独立危险因素。因此，人们对开发特异性升高HDL胆固醇的新疗法有相当大的兴趣。然而，最近的证据表明，仅仅增加循环HDL胆固醇水平作为HDL治疗的模式是不够的。相反，增加HDL功能特性的治疗方法可能上级简单地提高HDL本身的水平。我们实验室率先开发了合成的载脂蛋白模拟肽，其结构和功能与apoA-I相似，但与apoA-I的脂质相关结构域具有独特的结构同源性。apoA-I模拟肽4F抑制动脉粥样硬化小鼠模型中的致动脉粥样硬化病变形成。该效应与4F诱导富含apoA-I和对氧磷酶的前β HDL颗粒形成的能力有关。4F还具有抗炎和抗氧化特性，这些特性与其对HDL质量本身的影响无关。最近的研究表明，4F刺激抗氧化酶血红素加氧酶和超氧化物歧化酶的表达，并抑制糖尿病，高胆固醇血症和镰状细胞病小鼠血管中超氧阴离子的形成。本文综述了apoA-I模拟肽减轻实验动物血管损伤的HDL依赖性和非HDL依赖性机制。
Anti-atherogenic effects of high density lipoprotein (HDL) and its major protein component apolipoprotein A-I (apoA-I) are principally thought to be due to their ability to mediate reverse cholesterol transport. These agents also possess anti-oxidant properties that prevent the oxidative modification of low density lipoprotein (LDL) and anti-inflammatory properties that include inhibition of endothelial cell adhesion molecule expression. Results of the Framingham study revealed that a reduction in HDL levels is an independent risk factor for coronary artery disease (CAD). Accordingly, there has been considerable interest in developing new therapies that specifically elevate HDL cholesterol. However, recent evidence suggests that increasing circulating HDL cholesterol levels alone is not sufficient as a mode of HDL therapy. Rather, therapeutic approaches that increase the functional properties of HDL may be superior to simply raising the levels of HDL per se. Our laboratory has pioneered the development of synthetic, apolipoprotein mimetic peptides which are structurally and functionally similar to apoA-I but possess unique structural homology to the lipid-associating domains of apoA-I. The apoA-I mimetic peptide 4F inhibits atherogenic lesion formation in murine models of atherosclerosis. This effect is related to the ability of 4F to induce the formation of pre-β HDL particles that are enriched in apoA-I and paraoxonase. 4F also possesses anti-inflammatory and anti-oxidant properties that are independent of its effect on HDL quality per se. Recent studies suggest that 4F stimulates the expression of the antioxidant enzymes heme oxygenase and superoxide dismutase and inhibits superoxide anion formation in blood vessels of diabetic, hypercholesterolemic and sickle cell disease mice. The goal of this review is to discuss HDL-dependent and -independent mechanisms by which apoA-I mimetic peptides reduce vascular injury in experimental animal models.