ATRQβ-001 vaccine prevents atherosclerosis in apolipoprotein E-null mice.

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.