ATRQ beta-001 Vaccine Prevents Experimental Abdominal Aortic Aneurysms
ATRQ beta-001 Vaccine Prevents Experimental Abdominal Aortic Aneurysms
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ATRQ beta-001 疫苗可预防实验性腹主动脉瘤
DOI：
10.1161/jaha.119.012341
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发表时间：
2019
影响因子：
5.4
通讯作者：
Chen Xiao
中科院分区：
文献类型：
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作者：
Zhang Hongrong;Liao Mengyang;Cao Mingsi;Qiu Zhihua;Yan Xiaole;Zhou Yanzhao;Wu Hailang;Wang Yingxuan;Zheng Jiayu;Ding Jiaxing;Wang Min;Liao Yuhua;Chen Xiao
研究背景我们研制了一种肽疫苗ATRQβ-001，它被证明可以阻滞血管紧张素II（angiotensin II，Ang II）启动的信号转导。Ang II与腹主动脉瘤（AAA）的进展有关，但ATRQβ-001疫苗是否能预防AAA还不清楚。方法和结果使用Ang II输注的ApoE−/−小鼠和磷酸钙诱导的C57 BL/6小鼠AAA来验证ATRQβ-001疫苗在AAA中的有效性。结果表明，疫苗在两种动物模型中均有效抑制了主动脉的血管扩张和血管壁破坏，且不具有降压作用。在Ang II诱导的AAA血管切片中，免疫组织化学染色显示疫苗显著抑制血管炎症和血管平滑肌细胞（VSMC）表型转变，同时减少巨噬细胞浸润。在培养的VSMC中，抗ATR-001抗体抑制由Ang II诱导的骨桥蛋白分泌，从而在共培养时阻碍巨噬细胞迁移。结论ATRQ β-001疫苗在Ang II和磷酸钙诱导的AAA模型中均能抑制AAA的发生和发展。并发挥了降压以外的有益作用，为预防AAA提供了一种新的有前途的方法。
BackgroundWe have developed a peptide vaccine named ATRQβ‐001, which was proved to retard signal transduction initiated by angiotensin II (Ang II). Ang II was implicated in abdominal aortic aneurysm (AAA) progression, but whether the ATRQβ‐001 vaccine would prevent AAA is unknown.Methods and ResultsAng II‐infused ApoE−/−mice and calcium phosphate‐induced AAA in C57BL/6 mice were used to verify the efficiency of ATRQβ‐001 vaccine in AAA. Results demonstrated that the vaccine effectively restrained the aneurysmal dilation and vascular wall destruction of aorta in both animal models, beyond anti‐hypertensive effects. In Ang II‐induced AAA vascular sections, Immunohistochemical staining showed that the vaccine notably constrained vascular inflammation and vascular smooth muscle cell (VSMC) phenotypic transition, concurrently reduced macrophages infiltration. In cultured VSMC, the anti‐ATR‐001 antibody inhibited osteopontin secretion induced by Ang II, thereby impeded macrophage migration while co‐culture. Furthermore, metalloproteinases and other matrix proteolytic enzymes were also found to be limited by the vaccine in vivo and in vitro.ConclusionsATRQβ‐001 vaccine prevented AAA initiation and progression in both Ang II and calcium phosphate‐induced AAA models. And the beneficial effects were played beyond decrease of blood pressure, which provided a novel and promising method to take precautions against AAA.