A bivalent antihypertensive vaccine targeting L-type calcium channels and angiotensin AT1 receptors.
A bivalent antihypertensive vaccine targeting L-type calcium channels and angiotensin AT1 receptors.
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一种针对 L 型钙通道和血管紧张素 AT1 受体的二价抗高血压疫苗。
DOI：
10.1111/bph.14875
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发表时间：
2019
影响因子：
7.3
通讯作者：
Xiao Chen
中科院分区：
文献类型：
--
作者：
Hailang Wu;Yiyi Wang;Yuhua Liao;Xiao Chen
背景和目的：高血压是世界范围内可预防的过早死亡的主要原因。这项研究的目的是设计一种针对新靶点的更有效的疫苗，用于治疗高血压。实验方法：设计来自人L型钙通道（CaV 1.2）的表位CE 12，并将其与Qβ噬菌体病毒样颗粒缀合，以测试在高血压动物中的功效。此外，开发了乙型肝炎B核心抗原（HBcAg）-CE 12-CQ 10疫苗，这是一种基于HBcAg病毒样颗粒的双价疫苗，靶向人血管紧张素AT 1受体和CaV 1.2通道，并在高血压啮齿动物中进行了评价。关键结果：Qβ-CE 12疫苗有效降低高血压啮齿动物的血压。针对CE 12的单克隆抗体特异性结合L型钙通道并抑制通道活性。注射抗CE 12单克隆抗体可有效降低血管紧张素II诱导的高血压小鼠的血压。HBcAg-CE 12-CQ 10疫苗在高血压小鼠中显示出抗高血压作用，在自发性高血压大鼠中显示出相对较好的上级抗高血压作用，并改善L-NAME诱导的肾损伤。此外，未检测到明显的免疫介导的损伤或电生理不良反应。结论和意义：针对AT 1受体和CaV 1.2通道的免疫治疗有效地降低了高血压啮齿动物的血压，并提供了对高血压靶器官损害的保护，而没有明显的反馈激活肾素-血管紧张素系统或诱导针对载体蛋白的显性抗体。因此，HBcAg-CE 12-CQ 10疫苗可能为高血压提供一种新的和有前途的治疗方法。
BACKGROUND AND PURPOSE:.Hypertension has been the leading preventable cause of premature death worldwide. The aim of this study was to design a more efficient vaccine against novel targets for the treatment of hypertension...EXPERIMENTAL APPROACH:.The epitope CE12, derived from the human L-type calcium channel (CaV 1.2), was designed and conjugated with Qβ bacteriophage virus-like particles to test the efficacy in hypertensive animals. Further, the hepatitis B core antigen (HBcAg)-CE12-CQ10 vaccine, a bivalent vaccine based on HBcAg virus-like particles and targeting both human angiotensin AT1 receptors and CaV 1.2 channels, was developed and evaluated in hypertensive rodents...KEY RESULTS:.The Qβ-CE12 vaccine effectively decreased the BP in hypertensive rodents. A monoclonal antibody against CE12 specifically bound to L-type calcium channels and inhibited channel activity. Injection with monoclonal antibody against CE12 effectively reduced the BP in angiotensin II-induced hypertensive mice. The HBcAg-CE12-CQ10 vaccine showed antihypertensive effects in hypertensive mice and relatively superior antihypertensive effects in spontaneously hypertensive rats and ameliorated L-NAME-induced renal injury. In addition, no obvious immune-mediated damage or electrophysiological adverse effects were detected...CONCLUSION AND IMPLICATIONS:.Immunotherapy against both AT1 receptors and CaV 1.2 channels decreased the BP in hypertensive rodents effectively and provided protection against hypertensive target organ damage without obvious feedback activation of renin-angiotensin system or induction of dominant antibodies against the carrier protein. Thus, the HBcAg-CE12-CQ10 vaccine may provide a novel and promising therapeutic approach for hypertension.