A CD31-derived peptide prevents angiotensin II-induced atherosclerosis progression and aneurysm formation
A CD31-derived peptide prevents angiotensin II-induced atherosclerosis progression and aneurysm formation
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DOI：
10.1093/cvr/cvs076
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发表时间：
2012-04-01
影响因子：
10.8
通讯作者：
Caligiuri, Giuseppina
中科院分区：
文献类型：
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作者：
Fornasa, Giulia;Clement, Marc;Caligiuri, Giuseppina
外周T淋巴细胞上抑制受体CD31的缺失与动脉粥样硬化并发症的发生有关，如患者的腹主动脉瘤(AAA)和小鼠的斑块血栓形成。然而，我们最近发现，在明显为oCD31阴性的T细胞表面，仍有一小部分胞外CD31表达，利用合成的CD31衍生多肽，有可能在体内恢复CD31介导的T细胞抑制。在此，我们想要评估该肽在加速动脉粥样硬化和AA形成的实验模型中的治疗潜力。我们评价了小鼠CD31衍生肽(AA 551574，1.5 mg/kg/天，sc)对28周龄ApoE基因敲除小鼠(雄性，n epsilon 8/组)接受慢性血管紧张素II注射后动脉粥样硬化斑块的程度和AAA发生率的影响。通过评价其对体内、外免疫细胞功能的影响，探讨其治疗机制。血管紧张素II诱导的AAA的发生率与T细胞上细胞外CD31的丢失有关。CD31多肽治疗减少了动脉瘤的形成和斑块大小(与对照组相比，P<0.05)。保护与减少血管周围白细胞的渗透和体内T细胞的激活有关。体外功能研究表明，CD31多肽能够抑制T细胞和巨噬细胞的激活。CD31多肽可以代表一类新的药物，旨在防止炎症细胞过程，如那些潜在的动脉粥样硬化进展和AAA的发展。
The loss of the inhibitory receptor CD31 on peripheral T lymphocytes is associated with the incidence of atherosclerotic complications such as abdominal aortic aneurysms (AAA) in patients and plaque thrombosis in mice. However, we have recently discovered that a small fragment of extracellular CD31 remains expressed on the surface of the apparently oCD31-negative' T-cells and that it is possible to restore the CD31-mediated T-cell inhibition in vivo by using a synthetic CD31-derived peptide. Here, we wanted to evaluate the therapeutic potential of the peptide in an experimental model of accelerated atherosclerosis and AAA formation.The effect of the murine CD31-derived peptide (aa 551574, 1.5 mg/kg/day, sc) was evaluated on the extent of atherosclerotic plaques and the incidence of AAA in 28-week-old apolipoprotein E knockout mice (male, n epsilon 8/group) submitted to chronic angiotensin II infusion. The therapeutic mechanisms of the peptide were assessed by evaluating its effect on immune cell functions in vivo and in vitro. The prevalence of angiotensin II-induced AAA correlated with the loss of extracellular CD31 on T-cells. CD31 peptide treatment reduced both aneurysm formation and plaque size (P 0.05 vs. control). Protection was associated with reduced perivascular leucocyte infiltration and T-cell activation in vivo. Functional in vitro studies showed that the peptide is able to suppress both T-cell and macrophage activation.CD31 peptides could represent a new class of drugs intended to prevent the inflammatory cell processes, such as those underlying progression of atherosclerosis and development of AAA.