A peptide vaccine targeting angiotensin II attenuates the cardiac dysfunction induced by myocardial infarction

Ryo Watanabe, Jun-ichi Suzuki, Kouji Wakayama, Yasuhiro Maejima, Munehisa Shimamura, Hiroshi Koriyama, Hironori Nakagami, Hidetoshi Kumagai, Yuichi Ikeda, Hiroshi Akazawa, Ryuichi Morishita, Issei Komuro (+1 others)
2017 Scientific Reports  
A peptide vaccine targeting angiotensin II (Ang II) was recently developed as a novel treatment for hypertension to resolve the problem of noncompliance with pharmacotherapy. Ang II plays a crucial role in the pathogenesis of cardiac remodeling after myocardial infarction (MI), which causes heart failure. In the present study, we examined whether the Ang II vaccine is effective in preventing heart failure. The injection of the Ang II vaccine in a rat model of MI attenuated cardiac dysfunction
more » ... association with an elevation in the serum anti-Ang II antibody titer. Furthermore, any detrimental effects of the Ang II vaccine were not observed in the rats that underwent sham operations. Treatment with immunized serum from Ang II vaccine-injected rats significantly suppressed post-MI cardiac dysfunction in MI rats and Ang II-induced remodeling-associated signaling in cardiac fibroblasts. Thus, our present study demonstrates that the Ang II vaccine may provide a promising novel therapeutic strategy for preventing heart failure. The renin-angiotensin system (RAS) plays a pivotal role in the control of blood pressure and cardiovascular physiology. Angiotensin II (Ang), the primary component of RAS, induces hypertension via an Ang II type 1 receptor (AT1R). The chemical drugs that target Ang II, such as angiotensin converting enzyme inhibitor (ACEi) and angiotensin II receptor blocker (ARB), have therefore been widely used as antihypertensive drugs 1 . However, the control of blood pressure is often insufficient due to non-compliance 2 . The increase of the economic burden associated with lifelong medication may be another factor in non-compliance 2 . To resolve these problems and to improve therapeutic effects, a vaccine targeting the RAS was developed as a novel strategy for treating hypertension 3, 4 . Vaccine treatment is superior due to the duration of its effectiveness in comparison to chemical drugs; it may also be less expensive than conventional medications. Our previous study revealed that treatment with the Ang II vaccine (the conjugate of Ang II and keyhole limpet hemocyanin (KLH)) led to the production of anti-Ang II antibodies and reduced blood pressure in rodent models of hypertension 5 . The harmful effects of Ang II via AT1R induce not only hypertension but also inflammatory, hypertrophic, and fibrotic reactions 6, 7 . These effects of Ang II are associated with the pathophysiology of cardiovascular disease. Ischemic heart disease, including myocardial infarction (MI), is associated with a high rate of mortality in humans 8 . MI induces morphological changes called remodeling, which leads to heart failure accompanied by infarct area extension and thinning and compensatory hypertrophy of the non-infarcted myocardium [9] [10] [11] . Ang II-induced reactions may further damage the myocardium and accelerate post-MI remodeling 12 . In fact, ACEi and ARB have been shown to suppress the
doi:10.1038/srep43920 pmid:28266578 pmcid:PMC5339733 fatcat:xiu2b7wbnvhx7ljbqq2sj4i3e4