ATRQβ-001 vaccine prevents atherosclerosis in apolipoprotein E-null mice
ATRQβ-001 vaccine prevents atherosclerosis in apolipoprotein E-null mice
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ATRQ beta-001 疫苗可预防载脂蛋白 E 缺失小鼠的动脉粥样硬化
DOI：
10.1097/hjh.0000000000000835
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发表时间：
2016-03-01
影响因子：
4.9
通讯作者：
Chen, Xiao
中科院分区：
文献类型：
--
作者：
Zhou, Yanzhao;Wang, Shijia;Chen, Xiao
目的：血管紧张素 II（AngII）1 型受体（AT₁R）阻滞剂已被证实可减轻动脉粥样硬化。此前，我们研发了 ATRQ - 001 疫苗，该疫苗对 AT₁R 显示出理想的阻断效果。本研究旨在探讨 ATRQ - 001 疫苗是否能预防载脂蛋白 E 基因敲除（ApoE⁻/⁻）小鼠发生动脉粥样硬化。
方法：对雄性 ApoE⁻/⁻小鼠给予 ATRQ - 001 疫苗、Q 病毒样颗粒、缬沙坦或赋形剂，持续 24 周。在体外实验中，人冠状动脉内皮细胞分别用抗 ATR - 001 抗体、中和抗体或缬沙坦预孵育 2 小时，然后用 AngII 处理 24 小时。采用组织学染色和分子生物学方法评估该疫苗的抗动脉粥样硬化作用。
结果：ATRQ - 001 疫苗显著减小了病变面积，促进了动脉粥样硬化斑块的稳定性。同时，ATRQ - 001 疫苗组巨噬细胞浸润以及黏附分子和单核细胞趋化蛋白 - 1 的表达明显降低。此外，该疫苗显著减少了 ApoE⁻/⁻小鼠病变部位的细胞凋亡。在体外实验中，抗 ATR - 001 抗体抑制了 AngII 诱导的内皮细胞凋亡。此外，ATRQ - 001 疫苗显著降低了主动脉中凝集素样氧化低密度脂蛋白受体 - 1 和 AT₁R 的表达。更重要的是，与缬沙坦组相比，疫苗组未引发血浆肾素 - 血管紧张素系统的明显反馈。
结论：研究结果表明，ATRQ - 001 疫苗可减缓 ApoE⁻/⁻小鼠动脉粥样硬化的进展，且不会引起肾素 - 血管紧张素系统的明显反馈。
Objective:Angiotensin II (AngII) type 1 receptor (AT(1)R) blockers have been proved to reduce atherosclerosis. Previously, we have invented ATRQ-001 vaccine which showed a desirable blocking effect for AT(1)R. The purpose of this study was to investigate whether ATRQ-001 vaccine would prevent atherosclerosis in apolipoprotein E-null (ApoE(-/-)) mice.Methods:Male ApoE(-/-) mice were administered with ATRQ-001 vaccine, Q virus-like particles, valsartan or vehicle over a period of 24 weeks. In vitro, human coronary artery endothelial cells preincubated with the anti-ATR-001 antibody, the neutralization antibody or valsartan for 2h, were treated with AngII for 24h. Histological stain and molecule biology methods were used to assess the atheroprotective effect of the vaccine.Results:ATRQ-001 vaccine significantly reduced the lesion area and promoted the stability of atherosclerotic plaque. Meanwhile, macrophage infiltration as well as the expressions of adhesion molecules and monocyte chemoattractant protein-1 was obviously decreased in the ATRQ-001 vaccine group. Additionally, the vaccine markedly reduced the apoptosis in the lesions of the ApoE(-/-) mice. In vitro, the anti-ATR-001 antibody inhibited endothelial apoptosis induced by AngII. Furthermore, ATRQ-001 vaccine exhibited a dramatical attenuation in the expressions of lectin-like oxidized low-density lipoprotein receptor-1 and AT(1)R in the aortic. More importantly, compared with the valsartan group, no obvious feedback of the plasma renin-angiotensin system was elicited in the vaccine group.Conclusion:The results demonstrated that ATRQ-001 vaccine reduced the progression of atherosclerosis in ApoE(-/-) mice without obvious feedback of renin-angiotensin system.