The ATRQ beta-001 vaccine improves cardiac function and prevents postinfarction cardiac remodeling in mice

摘要

We invented the ATRQ beta-001 hypertension vaccine, which targeted angiotensin II type 1 receptor (AT(1)R) and showed a desirable blocking effect for AT(1)R. The purpose of this study was to investigate whether the ATRQ beta-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 + ATRQ beta-001, and MI + valsartan. Mice were administered Qp virus-like particle (Q(3-VLP, 100 pg/time), ATRQ beta-001 vaccine (100 mu g/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 ATRQ beta-001 vaccine on cardiac function and cardiac remodeling was observed by following up for 1 week, 4 weeks, and 12 weeks post MI. The ATRQ beta-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 ATRQ beta-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 ATRQ beta-001 vaccine obviously mitigated myocardial inflammation, apoptosis, and fibrosis after AMI. Further, the ATRQ beta-001 vaccine significantly inhibited the TGF-beta 1/Smad2/3 signaling pathway. Assessment of the renin-angiotensin system (RAS) demonstrated that the ATRQ beta-001 vaccine did not cause obvious feedback of circulating RAS, but prominently attenuated the expression of AT(1) R, compared with the other groups at 4 and 12 weeks after AMI. In conclusion, the ATRQ beta-001 vaccine decreased mortality and improved cardiac function and remodeling after AMI.