Objective: Angiotensin II (AngII) type 1 receptor (AT1R) blockers have been proved to reduce atherosclerosis. Previously, we have invented ATRQβ-001 vaccine which showed a desirable blocking effect for AT1R. 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 AT1R 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.