Internal Medicine, Clinical and Experimental Immunology, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht, The Netherlands.
PLoS One. 2013 Jul 16;8(7):e68039. doi: 10.1371/journal.pone.0068039. Print 2013.
New strategies to overcome complications of cardiovascular diseases are needed. Since it has been demonstrated that atherosclerosis is an inflammatory disease, modulation of the immune system may be a promising approach. Previously, it was suggested that antibodies may confer protective effects on the development of atherosclerosis. In this study, we hypothesised that passive immunization with anti-oxLDL IgM antibodies specific for hypochlorite (HOCl) may be athero-protective in mice.
Monoclonal mouse IgM antibodies were produced and the antibody with specificity for hypochlorite-oxLDL (HOCl-oxLDL) (Moab A7S8) was selected. VH sequence determination revealed that Moab A7S8 is a natural IgM antibody. Atherosclerosis in LDLr(-/-) mice was induced by a perivascular collar placement around the right carotid artery in combination with feeding a high-fat diet. Subsequently, the mice were treated every six days with 500 µg Moab A7S8, non-relevant IgM or with PBS and the carotid arteries and aortic roots were studied for atherosclerosis. Passive immunization with this Moab A7S8 resulted in a significant reduced plaque volume formation in LDLr(-/-) mice when compared with PBS treatment (P = 0.002 and P = 0.035). Cholesterol levels decreased by 20% when mice were treated with Moab A7S8 compared to PBS. Furthermore, anti-oxLDL specific IgM and IgG antibody production increased significantly in the Moab A7S8 treated mice in comparison with PBS treated mice.
Our data show that passive immunization with a natural IgM antibody, directed to HOCl-oxLDL, can reduce atherosclerotic plaque development. We postulate that specific antibody therapy may be developed for use in human cardiovascular diseases.
需要寻找新的策略来克服心血管疾病的并发症。由于已经证明动脉粥样硬化是一种炎症性疾病，因此免疫系统的调节可能是一种很有前途的方法。此前有研究表明，抗体可能对动脉粥样硬化的发展具有保护作用。在本研究中，我们假设针对次氯酸（HOCl）修饰的 oxLDL 的抗 oxLDL IgM 抗体的被动免疫可能对小鼠具有抗动脉粥样硬化作用。
产生了单克隆小鼠 IgM 抗体，并选择了针对次氯酸-oxLDL（HOCl-oxLDL）的特异性抗体（Moab A7S8）。VH 序列测定表明，Moab A7S8 是一种天然 IgM 抗体。通过在右侧颈动脉周围放置血管周袖套并结合高脂饮食来诱导 LDLr（-/-）小鼠发生动脉粥样硬化。随后，每六天用 500µg Moab A7S8、非相关 IgM 或 PBS 对小鼠进行治疗，并研究颈动脉和主动脉根部的动脉粥样硬化情况。与 PBS 处理相比，用这种 Moab A7S8 进行被动免疫可使 LDLr（-/-）小鼠的斑块体积形成显著减少（P=0.002 和 P=0.035）。与 PBS 处理相比，Moab A7S8 处理的小鼠的胆固醇水平降低了 20%。此外，与 PBS 处理的小鼠相比，Moab A7S8 处理的小鼠中抗 oxLDL 的特异性 IgM 和 IgG 抗体的产生显著增加。
我们的数据表明，针对 HOCl-oxLDL 的天然 IgM 抗体的被动免疫可以减少动脉粥样硬化斑块的形成。我们推测，针对特定抗体的治疗方法可能会被开发用于人类心血管疾病。
