Mimetic peptides are potential therapeutic agents for atherosclerosis. d-[¹¹³,¹¹⁴,¹¹⁵,¹¹⁶,¹¹⁷,¹¹⁸,¹¹⁹,¹²⁰,¹²¹,¹²²]apolipoprotein (apo) J (D-[¹¹³,¹¹⁴,¹¹⁵,¹¹⁶,¹¹⁷,¹¹⁸,¹¹⁹,¹²⁰,¹²¹,¹²²]apoJ) is a 10-residue peptide that is predicted to form a class G* amphipathic helix 6 from apoJ; it shows anti-inflammatory and anti-atherogenic properties. In the present study, we analyzed the effect of d-[¹¹³,¹¹⁴,¹¹⁵,¹¹⁶,¹¹⁷,¹¹⁸,¹¹⁹,¹²⁰,¹²¹,¹²²]apoJ in low-density lipoprotein receptor knockout mice(LDLR-KO) on the development of atherosclerosis and lipoprotein function. Fifteen-week-old female LDLR-KO mice fed an atherogenic Western-type diet were treated for eight weeks with d-[¹¹³,¹¹⁴,¹¹⁵,¹¹⁶,¹¹⁷,¹¹⁸,¹¹⁹,¹²⁰,¹²¹,¹²²]apoJ peptide, a scrambled peptide, or vehicle. Peptides were administered subcutaneously three days per week (200 µg in 100 µL of saline). After euthanasia, blood and hearts were collected and the aortic arch was analyzed for the presence of atherosclerotic lesions. Lipoproteins were isolated and their composition and functionality were studied. The extent of atherosclerotic lesions was 43% lower with d-[¹¹³,¹¹⁴,¹¹⁵,¹¹⁶,¹¹⁷,¹¹⁸,¹¹⁹,¹²⁰,¹²¹,¹²²]apoJ treatment than with the vehicle or scramble. The lipid profile was similar between groups, but the high-density lipoprotein (HDL) of d-[¹¹³,¹¹⁴,¹¹⁵,¹¹⁶,¹¹⁷,¹¹⁸,¹¹⁹,¹²⁰,¹²¹,¹²²]apoJ-treated mice had a higher antioxidant capacity and increased ability to promote cholesterol efflux than the control group. In addition, low-density lipoprotein (LDL) from d-[¹¹³,¹¹⁴,¹¹⁵,¹¹⁶,¹¹⁷,¹¹⁸,¹¹⁹,¹²⁰,¹²¹,¹²²]apoJ-treated mice was more resistant to induced aggregation and presented lower electronegativity than in mice treated with d-[¹¹³,¹¹⁴,¹¹⁵,¹¹⁶,¹¹⁷,¹¹⁸,¹¹⁹,¹²⁰,¹²¹,¹²²]apoJ. Our results demonstrate that the d-[¹¹³,¹¹⁴,¹¹⁵,¹¹⁶,¹¹⁷,¹¹⁸,¹¹⁹,¹²⁰,¹²¹,¹²²]apoJ peptide prevents the extent of atherosclerotic lesions, which could be partially explained by the improvement of lipoprotein functionality.

中文翻译：

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皮下施用载脂蛋白J衍生的模拟肽d- [113-122] apoJ可改善LDLR-KO小鼠的LDL和HDL功能，并预防动脉粥样硬化。

模拟肽是动脉粥样硬化的潜在治疗剂。D- [ ¹¹³，¹¹⁴，¹¹⁵，¹¹⁶，¹¹⁷，¹¹⁸，¹¹⁹，¹²⁰，¹²¹，¹²² ]载脂蛋白（APO）.J（D- [ ¹¹³，¹¹⁴，¹¹⁵，¹¹⁶，¹¹⁷，¹¹⁸，¹¹⁹，¹²⁰，¹²¹，¹²²] apoJ）是10个残基的肽，预计会从apoJ形成G *类两亲性螺旋6；它具有抗炎和抗动脉粥样硬化特性。在本研究中，我们分析的效果D- [ ¹¹³，¹¹⁴，¹¹⁵，¹¹⁶，¹¹⁷，¹¹⁸，¹¹⁹，¹²⁰，¹²¹，¹²² ] apoJ在开发低密度脂蛋白受体敲除小鼠（LDLR-KO）动脉粥样硬化和脂蛋白的功能 十五周龄雌性LDLR-KO小鼠喂食致动脉粥样西方型饮食进行处理八周与D- [ ¹¹³，¹¹⁴，¹¹⁵，¹¹⁶，¹¹⁷，¹¹⁸，¹¹⁹，¹²⁰，¹²¹，¹²² ] apoJ肽，乱序肽，或赋形剂。每周三天皮下注射肽（100 µL盐水中200 µg）。安乐死后，收集血液和心脏，分析主动脉弓是否存在动脉粥样硬化病变。分离脂蛋白并研究其组成和功能。动脉粥样硬化的程度为43％与D- [降低¹¹³，¹¹⁴，¹¹⁵，¹¹⁶，¹¹⁷，¹¹⁸，¹¹⁹，¹²⁰，¹²¹，¹²² ] apoJ治疗比与车辆的加扰或。脂质分布为组之间是相似的，但在高密度脂蛋白（HDL）D- [的¹¹³，¹¹⁴，¹¹⁵，¹¹⁶，¹¹⁷，¹¹⁸，¹¹⁹，¹²⁰，¹²¹，¹²² ] apoJ处理的小鼠具有更高的抗氧化能力与促进胆固醇外排的能力相比，对照组更高。另外，从D- [低密度脂蛋白（LDL）¹¹³，¹¹⁴，¹¹⁵，¹¹⁶，¹¹⁷，¹¹⁸，¹¹⁹，¹²⁰，¹²¹，¹²² ] apoJ处理的小鼠是诱导的聚集更耐并呈现比在具有D- [处理的小鼠低的电负性¹¹³，¹¹⁴，¹¹⁵，¹¹⁶，¹¹⁷，¹¹⁸，¹¹⁹，¹²⁰，¹²¹，¹²² ]载脂蛋白 我们的研究结果表明，D- [ ¹¹³，¹¹⁴，¹¹⁵，¹¹⁶，¹¹⁷，¹¹⁸，¹¹⁹，¹²⁰，¹²¹，¹²² ] apoJ肽可预防动脉粥样硬化病变的程度，这可以部分由脂蛋白功能的改善来解释。