ATRQβ-001 vaccine prevents atherosclerosis in apolipoprotein E-null mice. Issue 3 (March 2016)

• Record Type: Journal Article
• Authors: Zhou, Yanzhao; Wang, Shijia; Qiu, Zhihua; Song, Xiaoxiao; Pan, Yajie; Hu, Xiajun; Zhang, Hongrong; Deng, Yihuan; Ding, Dan; Wu, Hailang; Yang, Shijun; Wang, Min; Zhou, Zihua; Liao, Yuhua; Chen, Xiao
• Is Part Of: Journal of hypertension. Volume 34:Issue 3(2016:Mar.)
• Publication Date: 2016-03
• Subjects: angiotensin II type 1 receptor -- apoptosis -- atherosclerosis -- lectin-like oxidized low-density lipoprotein receptor-1 -- vaccine; Hypertension -- Periodicals; Hypertension -- Periodicals; 616.132005
• DOI: 10.1097/HJH.0000000000000835
• Languages: English
• ISSNs: 1473-5598

Abstract

Abstract : Objective: Angiotensin II (AngII) type 1 receptor (AT1 R) blockers have been proved to reduce atherosclerosis. Previously, we have invented ATRQβ-001 vaccine which showed a desirable blocking effect for AT1 R. The purpose of this study was to investigate whether ATRQβ-001 vaccine would prevent atherosclerosis in apolipoprotein E-null (ApoE –/– ) mice. Methods: Male ApoE –/– mice were administered with ATRQβ-001 vaccine, Qβ 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 2 h, were treated with AngII for 24 h. Histological stain and molecule biology methods were used to assess the atheroprotective effect of the vaccine. Results: ATRQβ-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 ATRQβ-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, ATRQβ-001 vaccine exhibited a dramatical attenuation in the expressions of lectin-like oxidized low-density lipoprotein receptor-1 and AT1 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 ATRQβ-001 vaccine reduced the progression of atherosclerosis in ApoE –/– mice without obvious feedback of renin–angiotensin system. Abstract : Supplemental Digital Content is available in the text