Abstract 16969: Long Term Blood Pressure Reduction by Angiotensin II DNA Vaccine in Spontaneously Hypertensive Rats Model
Background: Recent progress on vaccination has extended its scope from infectious diseases to common disease such as Alzheimer’s disease, dyslipidemia and hypertension. The aim of this study is to design DNA vaccines for high blood pressure (BP) and eventually to develop human vaccine therapy to treat hypertension.
Method: We selected angiotensin II (Ang II) as a target antigen. Plasmid vector encoding Hepatitis B core (HBc)-Ang II fusion protein was constructed, as HBc forms sphere-like structure by self-aggregation and the integration of the target peptide in the surface region of HBc protein induces high titer antibody to the target peptide. Plasmid DNA (HBc-Ang II or HBc) or saline were injected to the back skin of spontaneously hypertensive rats (SHR) three times by needle-less injection system (n=6-8 rats per group).
Results: Anti-Ang II antibody was successfully produced in HBc-Ang II group and sustained at least up to 6 months. The titers of anti-Ang II and anti-Ang I antibodies significantly increased after immunization, while the titers of anti-angiotensinogen (AGT) and anti-Ang1-7 antibodies did not significantly increase. These results indicated that the immunization was specific to Ang I and Ang II. Consistently, systolic BP was lower in HBc-Ang II group after the immunization (at 12 weeks: 188.1 ± 15.8 mmHg in HBc-Ang II group vs. 221.5 ± 14.6 mmHg in HBc group, P<0.01), and BP reduction continued at least up to 6 months. It is noteworthy that a significant decrease in plasma Ang II concentration was observed in HBc-AngII group (-30 pg/ml, P<0.001 vs. HBc and saline group). Of importance, perivascular fibrosis in heart tissue was significantly reduced in HBc-Ang II group. Aortic media thickness reduction was also observed in HBc-AngII group.
T cell activity of cytokine production that responded to Ang II or AGT was not detected. Any pathological findings were not observed in tissue sections (kidney, heart, aorta, and liver) examined.
Conclusion: The present study demonstrated that Ang II DNA vaccine to SHR significantly lowered high BP at least up to 6 months and did not cause any hazardous autoimmune reactions. Future development of DNA vaccine to hypertension may provide new therapeutic option to treat hypertensive population.
- © 2013 by American Heart Association, Inc.