Anti-Apolipoprotein A-1 auto-antibodies are active mediators of atherosclerotic plaque vulnerability
Anti-Apolipoprotein A-1 auto-antibodies are active mediators of atherosclerotic plaque vulnerability
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DOI：
10.1093/eurheartj/ehq521
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发表时间：
2011-02-01
影响因子：
39.3
通讯作者：
Roux-Lombard, Pascale
中科院分区：
文献类型：
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作者：
Montecucco, Fabrizio;Vuilleumier, Nicolas;Roux-Lombard, Pascale
抗载脂蛋白A-1自身抗体（anti-ApoA-1 IgG）是心肌梗死或自身免疫性疾病患者心血管疾病高危的一种新的预后指标。抗ApoA-1 IgG和斑块易损性之间的潜在关系仍然难以捉摸。因此，我们的目的是探讨抗ApoA-1 IgG在斑块vulnerability.Methods和结果之间的潜在关系抗ApoA-1 IgG和功能的心血管脆弱性进行了探讨，在体内和体外的作用。在体内，我们研究了严重颈动脉狭窄患者（n=102）和多克隆抗ApoA-1 IgG输注的ApoE（-/-）小鼠中的抗ApoA-1 IgG。在体外，评估了抗ApoA-1 IgG对人原代巨噬细胞、单核细胞和中性粒细胞的作用。与相应对照组相比，抗ApoA-1 IgG阳性患者和抗ApoA-1 IgG治疗小鼠斑块内胶原减少，而中性粒细胞和基质金属蛋白酶（MMP）-9含量增加。在小鼠主动脉根部（但不是在腹主动脉瘤），与对照组相比，抗ApoA-1 IgG治疗与病变大小增加相关。在人类中，血清抗ApoA-1 IgG水平与斑块内巨噬细胞、中性粒细胞和MMP-9含量呈正相关，与胶原蛋白呈负相关。在体外实验中，抗ApoA-1 IgG可增加巨噬细胞释放CCL 2、CXCL 8和MMP-9，以及中性粒细胞向TNF-α或CXCL 8的迁移。结论抗ApoA-1 IgG可增加人和小鼠动脉粥样硬化斑块的易损性。
Aims Anti-Apolipoprotein A-1 auto-antibodies (anti-ApoA-1 IgG) represent an emerging prognostic cardiovascular marker in patients with myocardial infarction or autoimmune diseases associated with high cardiovascular risk. The potential relationship between anti-ApoA-1 IgG and plaque vulnerability remains elusive. Thus, we aimed to investigate the role of anti-ApoA-1 IgG in plaque vulnerability.Methods and results Potential relationship between anti-ApoA-1 IgG and features of cardiovascular vulnerability was explored both in vivo and in vitro. In vivo, we investigated anti-ApoA-1 IgG in patients with severe carotid stenosis (n=102) and in ApoE(-/-) mice infused with polyclonal anti-ApoA-1 IgG. In vitro, anti-ApoA-1 IgG effects were assessed on human primary macrophages, monocytes, and neutrophils. Intraplaque collagen was decreased, while neutrophil and matrix metalloprotease (MMP)-9 content were increased in anti-ApoA-1 IgG-positive patients and anti-ApoA-1 IgG-treated mice when compared with corresponding controls. In mouse aortic roots (but not in abdominal aortas), treatment with anti-ApoA-1 IgG was associated with increased lesion size when compared with controls. In humans, serum anti-ApoA-1 IgG levels positively correlated with intraplaque macrophage, neutrophil, and MMP-9 content, and inversely with collagen. In vitro, anti-ApoA-1 IgG increased macrophage release of CCL2, CXCL8, and MMP-9, as well as neutrophil migration towards TNF-alpha or CXCL8.Conclusion These results suggest that anti-ApoA-1 IgG might be associated with increased atherosclerotic plaque vulnerability in humans and mice.