Department of Medicine and Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Atherosclerosis. 2012 Oct;224(2):326-31. doi: 10.1016/j.atherosclerosis.2012.05.040. Epub 2012 Jun 23.
The apolipoprotein E mimetic peptide Ac-hE18A-NH(2), capable of reducing plasma cholesterol and possessing anti-inflammatory properties, was compared with the well-studied anti-atherogenic apoA-I mimetic peptide 4F for reducing lesion formation in female apoE null mice with already existing lesions.
In initial experiments, Ac-hE18A-NH(2) was administered retro-orbitally two or three times weekly for 6-8 weeks, while peptide 4F was administered intraperitoneally every day for the same period. Age matched controls were injected with saline every day. At the end of the treatment period, plasma cholesterol levels of Ac-hE18A-NH(2) administered mice were significantly lower than in 4F and control mice. However, both 4F and Ac-hE18A-NH(2) showed reduced lesion areas in en face lesion analysis to a similar extent compared to the control group, while paraoxonase-1 (PON-1) activity was increased only in the Ac-hE18A-NH(2) group. In the third experiment, both peptides were administered at the same dose, frequency, and route of administration. The reduction in en face lesions with Ac-hE18A-NH(2) was significantly greater than the 4F and control groups, although lesions in 4F-treated mice were also significantly reduced compared with controls. Both peptide groups had significantly reduced plasma lipid hydroperoxides, but only the Ac-hE18A-NH(2) group had significantly reduced serum amyloid A levels. HDL and plasma inflammatory indices were significantly reduced in both peptide groups compared with controls.
Although both peptides had similar anti-inflammatory properties, Ac-hE18A-NH(2) was more effective in inhibiting lesions than 4F at the same dose, frequency, and route of administration, perhaps due to its cholesterol reducing properties.
载脂蛋白 E 模拟肽 Ac-hE18A-NH(2) 能够降低血浆胆固醇，具有抗炎特性，与研究充分的载脂蛋白 A-I 模拟肽 4F 进行了比较，以观察其在已经存在病变的雌性载脂蛋白 E 基因敲除小鼠中减少病变形成的效果。
在最初的实验中，Ac-hE18A-NH(2) 通过每周两次或三次经眶后给药，持续 6-8 周，而肽 4F 则通过腹腔内注射，给药时间相同。年龄匹配的对照组每天注射生理盐水。在治疗期末，给予 Ac-hE18A-NH(2) 的小鼠的血浆胆固醇水平明显低于 4F 和对照组的小鼠。然而，与对照组相比，4F 和 Ac-hE18A-NH(2) 都使正面病变分析中的病变面积显著减少，而只有 Ac-hE18A-NH(2) 组的对氧磷酶-1 (PON-1) 活性增加。在第三个实验中，以相同的剂量、频率和给药途径给予两种肽。与 4F 和对照组相比，Ac-hE18A-NH(2) 给药组的正面病变减少更为显著，尽管 4F 治疗组的病变也比对照组显著减少。两种肽组的血浆脂质氢过氧化物都显著减少，但只有 Ac-hE18A-NH(2) 组的血清淀粉样蛋白 A 水平显著降低。与对照组相比，两种肽组的 HDL 和血浆炎症指数均显著降低。
尽管两种肽都具有相似的抗炎特性，但在相同剂量、频率和给药途径下，Ac-hE18A-NH(2) 抑制病变的效果优于 4F，这可能是由于其降低胆固醇的特性。
