Long-Term Reduction of High Blood Pressure by Angiotensin II DNA Vaccine in Spontaneously Hypertensive Rats
Long-Term Reduction of High Blood Pressure by Angiotensin II DNA Vaccine in Spontaneously Hypertensive Rats
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DOI：
10.1161/hypertensionaha.114.04534
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发表时间：
2015-07-01
期刊：
影响因子：
8.3
通讯作者：
Morishita, Ryuichi
中科院分区：
文献类型：
--
作者：
Koriyama, Hiroshi;Nakagami, Hironori;Morishita, Ryuichi
最近关于疫苗接种的研究已经将其范围从传染病扩展到慢性病，包括阿尔茨海默病、血脂异常和高血压。这项研究的目的是设计高血压的DNA疫苗，并最终开发出治疗高血压的人类疫苗疗法。采用无针注射系统将编码乙肝核心-血管紧张素II(Ang II)融合蛋白的质粒载体注射到自发性高血压大鼠体内。乙肝核心-血管紧张素Ⅱ组成功产生抗血管紧张素Ⅱ抗体，且抗体应答持续至少6个月。乙肝核心II组免疫后收缩压持续降低，但持续降压至少6个月。乙肝核心血管II组心脏组织血管周围纤维化也明显减轻。乙肝核心血管紧张素Ⅱ组存活率明显提高。这项研究表明，自发性高血压大鼠的Ang II DNA疫苗至少在6个月内显著降低高血压。此外，通过ELISPOT分析，Ang II DNA疫苗诱导了足够的体液免疫反应，同时避免了自身反应性T细胞的激活。未来用于治疗高血压的DNA疫苗的发展可能为治疗高血压提供一种新的治疗选择。
Recent research on vaccination has extended its scope from infectious diseases to chronic diseases, including Alzheimer disease, dyslipidemia, and hypertension. The aim of this study was to design DNA vaccines for high blood pressure and eventually develop human vaccine therapy to treat hypertension. Plasmid vector encoding hepatitis B core-angiotensin II (Ang II) fusion protein was injected into spontaneously hypertensive rats using needleless injection system. Anti-Ang II antibody was successfully produced in hepatitis B core-Ang II group, and antibody response against Ang II was sustained for at least 6 months. Systolic blood pressure was consistently lower in hepatitis B core-Ang II group after immunization, whereas blood pressure reduction was continued for at least 6 months. Perivascular fibrosis in heart tissue was also significantly decreased in hepatitis B core-Ang II group. Survival rate was significantly improved in hepatitis B core-Ang II group. This study demonstrated that Ang II DNA vaccine to spontaneously hypertensive rats significantly lowered high blood pressure for at least 6 months. In addition, Ang II DNA vaccines induced an adequate humoral immune response while avoiding the activation of self-reactive T cells, assessed by ELISPOT assay. Future development of DNA vaccine to treat hypertension may provide a new therapeutic option to treat hypertension.