Leung Viola W Y, Yun Sheng, Botto Marina, Mason Justin C, Malik Talat H, Song Wenchao, Paixao-Cavalcante Danielle, Pickering Matthew C, Boyle Joseph J, Haskard Dorian O
Vascular Science Section, Imperial College, National Heart and Lung Institute, the Division of Investigative Sciences, Imperial College London, Hammersmith Hospital, London W12 0NN, United Kingdom.
Am J Pathol. 2009 Oct;175(4):1757-67. doi: 10.2353/ajpath.2009.090183. Epub 2009 Sep 3.
Decay-accelerating factor (DAF; CD55) is a membrane protein that regulates complement pathway activity at the level of C3. To test the hypothesis that DAF plays an essential role in limiting complement activation in the arterial wall and protecting from atherosclerosis, we crossed DAF gene targeted mice (daf-1(-/-)) with low-density lipoprotein-receptor deficient mice (Ldlr(-/-)). Daf-1(-/-)Ldlr(-/-) mice had more extensive en face Sudan IV staining of the thoracoabdominal aorta than Ldlr(-/-) mice, both following a 12-week period of low-fat diet or a high-fat diet. Aortic root lesions in daf-1(-/-)Ldlr(-/-) mice on a low-fat diet showed increased size and complexity. DAF deficiency increased deposition of C3d and C5b-9, indicating the importance of DAF for downstream complement regulation in the arterial wall. The acceleration of lesion development in the absence of DAF provides confirmation of the proinflammatory and proatherosclerotic potential of complement activation in the Ldlr(-/-) mouse model. Because upstream complement activation is potentially protective, this study underlines the importance of DAF in shielding the arterial wall from the atherogenic effects of complement.
衰变加速因子（DAF；CD55）是一种膜蛋白，可在C3水平调节补体途径活性。为了验证DAF在限制动脉壁补体激活和预防动脉粥样硬化中起关键作用这一假说，我们将DAF基因靶向小鼠（daf-1(-/-)）与低密度脂蛋白受体缺陷小鼠（Ldlr(-/-)）进行杂交。在低脂饮食或高脂饮食12周后，daf-1(-/-)Ldlr(-/-)小鼠胸腹主动脉的苏丹IV整体染色比Ldlr(-/-)小鼠更广泛。低脂饮食的daf-1(-/-)Ldlr(-/-)小鼠主动脉根部病变的大小和复杂性增加。DAF缺陷增加了C3d和C5b-9的沉积，表明DAF对动脉壁下游补体调节的重要性。在缺乏DAF的情况下病变发展加速，证实了Ldlr(-/-)小鼠模型中补体激活的促炎和促动脉粥样硬化潜力。由于上游补体激活可能具有保护作用，本研究强调了DAF在保护动脉壁免受补体致动脉粥样硬化作用方面的重要性。
