Treatment with apo B peptide vaccines inhibits atherosclerosis in human apo B-100 transgenic mice without inducing an increase in peptide-specific antibodies
Treatment with apo B peptide vaccines inhibits atherosclerosis in human apo B-100 transgenic mice without inducing an increase in peptide-specific antibodies
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DOI：
10.1111/j.1365-2796.2008.01995.x
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发表时间：
2008-12-01
影响因子：
11.1
通讯作者：
Nilsson, J.
中科院分区：
文献类型：
--
作者：
Fredrikson, G. N.;Borkbacka, H.;Nilsson, J.
载脂蛋白（apo）B-100肽的自身抗体存在于人血浆中，并已显示与心血管风险降低相关。本研究旨在确定apo B-100肽疫苗在表达人apo B-100的小鼠中是否具有动脉粥样硬化保护作用，以及疫苗的有效性是否受到预先存在的肽特异性自身抗体水平的影响。9和11周，并在25周通过主动脉的表面油红O染色确定动脉粥样硬化的程度。自身抗体水平通过酶联免疫吸附测定法测定，脾脏RNA表达通过真实的时间PCR进行评估。对照小鼠具有高水平的抗p210的自身抗体，但仅具有低水平的抗p45的自身抗体。用天然p45和p210免疫分别使动脉粥样硬化减少66%（P < 0.02）和59%（P = 0.06）。载脂蛋白B肽免疫的动脉粥样硬化保护作用发生在肽特异性IgG增加的情况下，但与IgM识别天然和铜氧化LDL.Immunization与载脂蛋白B肽为基础的疫苗的增加抑制表达人载脂蛋白B-100的小鼠动脉粥样硬化表明，他们可以与他们的目标在人类表达。这种保护作用不依赖于载脂蛋白B肽自身抗体的预先存在水平，并且可以在不激活肽特异性抗体增加的情况下发生，这表明动脉粥样硬化保护作用可以由细胞免疫应答介导。
Autoantibodies to apolipoprotein (apo) B-100 peptides are present in human plasma and have been shown to be associated with decreased cardiovascular risk. The present study aimed to determine if apo B-100 peptide vaccines are atheroprotective in mice expressing human apo B-100 and if the effectiveness of the vaccines is influenced by the level of pre-existing peptide-specific autoantibodies.LDL receptor(-/-)/human apo B-100 transgenic mice were immunized with native human apo B-100 peptides p45 or p210 at 6, 9 and 11 weeks and the extent of atherosclerosis determined by en face Oil Red O staining of the aorta at 25 weeks. Autoantibody levels were determined by enzyme-linked immunosorbent assay, and RNA expression in the spleen was assessed by real time PCR.Control mice had high levels of autoantibodies against p210 but only low levels against p45. Immunization with native p45 and p210 reduced atherosclerosis by 66% (P < 0.02) and 59% (P = 0.06), respectively. The atheroprotective effect of apo B peptide immunization occurred in the absence of an increase in peptide-specific IgG, but was associated with an increase in IgM recognizing native and copper-oxidized LDL.Immunization with apo B peptide-based vaccines inhibits atherosclerosis in mice expressing human apo B-100 suggesting that they can interact with their target as expressed in humans. The protective effect is independent of the pre-existing level of apo B peptide autoantibodies and can occur without activating an increase in peptide-specific antibodies suggesting that atheroprotection can be mediated by cellular immune responses.