We invented the ATRQβ-001 hypertension vaccine, which targeted angiotensin II type 1 receptor (AT1R) and showed a desirable blocking effect for AT1R. The purpose of this study was to investigate whether the ATRQβ-001 vaccine could improve cardiac function and prevent cardiac remodeling after acute myocardial infarction (AMI). C57BL/6 male mice were randomly assigned into four groups: sham + VLP, MI + VLP, MI + ATRQβ-001, and MI + valsartan. Mice were administered Qβ virus-like particle (Qβ-VLP, 100 μg/time), ATRQβ-001 vaccine (100 μg/time), and valsartan (6 mg/kg/day) before AMI, which was induced by permanently ligating the left anterior descending coronary artery. The effect of the ATRQβ-001 vaccine on cardiac function and cardiac remodeling was observed by following up for 1 week, 4 weeks, and 12 weeks post MI. The ATRQβ-001 vaccine significantly reduced sudden cardiac death and increased survival rates (compared with MI + VLP, 80% versus 55% and mean estimate (days) 68.4 ± 7.0 versus 47.8 ± 8.9, respectively; p = 0.046) post MI. Echocardiography showed that the ATRQβ-001 vaccine remarkably improved cardiac function (left ventricular ejection fraction, 24.8 ± 7.0% versus 13.2 ± 3.8%, p = 0.005) post MI. Histological analysis revealed that the ATRQβ-001 vaccine obviously mitigated myocardial inflammation, apoptosis, and fibrosis after AMI. Further, the ATRQβ-001 vaccine significantly inhibited the TGF-β1/Smad2/3 signaling pathway. Assessment of the renin-angiotensin system (RAS) demonstrated that the ATRQβ-001 vaccine did not cause obvious feedback of circulating RAS, but prominently attenuated the expression of AT1R, compared with the other groups at 4 and 12 weeks after AMI. In conclusion, the ATRQβ-001 vaccine decreased mortality and improved cardiac function and remodeling after AMI.
Keywords: ATRQβ-001 vaccine; Acute myocardial infarction; Angiotensin II receptor; Cardiac remodeling.