title: Effectiveness and safety of a therapeutic vaccine against angiotensin II receptor type 1 in hypertensive animals.
abstract: Primary hypertension is a chronic disease with high morbidity, and the rate of controlled blood pressure is far from satisfactory, worldwide. Vaccination provides a promising approach for treatment of hypertension and improvement in compliance. Here, the ATRQβ-001 vaccine, a peptide (ATR-001) derived from human angiotensin II (Ang II) receptor type 1 conjugated with Qβ bacteriophage virus-like particles, was developed and evaluated in animal models of hypertension. The ATRQβ-001 vaccine significantly decreased the blood pressure of Ang II-induced hypertensive mice up to 35 mm Hg (143 ± 4 versus 178 ± 6 mm Hg; P=0.005) and that of spontaneously hypertensive rats up to 19 mm Hg (173 ± 2 versus 192 ± 3 mm Hg; P=0.003) and prevented remodeling of vulnerable hypertensive target organs. No obvious feedback activation of circulating or local renin-angiotensin system was observed. Additionally, no significant immune-mediated damage was detected in vaccinated hypertensive and nonhypertensive animals. The half-life of the anti-ATR-001 antibody was 14.4 days, surpassing that of existing chemical drugs. In vitro, the anti-ATR-001 antibody specifically bound to Ang II receptor type 1 and inhibited Ca(2+)-dependent signal transduction events, including protein kinase C-α translocation, extracellular signal-regulated kinase 1/2 phosphorylation (72% decrease; P=0.013), and elevation of intracellular Ca(2+) (68% decrease; P=0.017) induced by Ang II, but without inhibiting Ang II binding to the receptor. In conclusion, the ATRQβ-001 vaccine decreased the blood pressure of Ang II-induced hypertensive mice and spontaneously hypertensive rats effectively through diminishing the pressure response and inhibiting signal transduction initiated by Ang II. Thus, the ATRQβ-001 vaccine may provide a novel and promising method for the treatment of primary hypertension.
authors.affiliation: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Chen
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Qiu
authors.forename: Shijun
authors.initials: S
authors.lastname: Yang
authors.forename: Dan
authors.initials: D
authors.lastname: Ding
authors.forename: Fen
authors.initials: F
authors.lastname: Chen
authors.forename: Yanzhao
authors.initials: Y
authors.lastname: Zhou
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.forename: Jibin
authors.initials: J
authors.lastname: Lin
authors.forename: Xian
authors.initials: X
authors.lastname: Yu
authors.forename: Zihua
authors.initials: Z
authors.lastname: Zhou
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Liao
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000502:physiology*; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D051379:Mice; D010766:Phosphorylation; D051381:Rats; D011918:Rats, Inbred SHR; D044140:Receptor, Angiotensin, Type 1 / Q000276:immunology*; D012084:Renin-Angiotensin System / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D014611:Vaccination / Q000009:adverse effects*; D014612:Vaccines
chemical_list: D044140:Receptor, Angiotensin, Type 1; D014612:Vaccines