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      Decrease in Blood Pressure and Regression of Cardiovascular Complications by Angiotensin II Vaccine in Mice

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          Abstract

          Vaccines have been recently developed to treat various diseases such as cancer, rheumatoid arthritis and Alzheimer’s disease in addition to infectious diseases. However, before use in the clinical setting, vaccines targeting self-antigens must be demonstrated to be effective and safe, evoking an adequate humoral immune response from B cells while avoiding T cell activation in response to self. Although the vaccine targeting angiotensin II (Ang II) is efficient in rodents and humans, little is known regarding the immunological activation and safety of the vaccine. In this study, we evaluated the efficiency and safety of an Ang II peptide vaccine in mice. Immunization with Ang II conjugated to keyhole limpet hemocyanin (KLH) successfully induced the production of anti-Ang II antibody, which blocked Ang II signaling in human aortic smooth muscle cells. However, Ang II itself did not activate T cells, as assessed by the proliferation and lymphokine production of T cells in immunized mice, whereas KLH activated T cells. In an Ang II-infused model, the non-immunized mice showed high blood pressure (BP), whereas the immunized mice (Ang II-KLH) showed a significant decrease in systolic BP, accompanied by significant reductions in cardiac hypertrophy and fibrosis. Importantly, anti-Ang II antibody titer was not elevated even after the administration of large amounts of Ang II, indicating that Ang II itself boosted antibody production, most likely due to less activation of T cells. In addition, no accumulation of inflammatory cells was observed in immunized mice, because endogenous Ang II would not activate T cells after immunization with Ang II-KLH. Taken together, these data indicate that vaccines targeting Ang II might be effective to decrease high BP and prevent cardiovascular complications without severe side effects.

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          Author and article information

          Contributors
          Role: Editor
          Journal
          PLoS One
          PLoS ONE
          plos
          plosone
          PLoS ONE
          Public Library of Science (San Francisco, USA )
          1932-6203
          2013
          27 March 2013
          : 8
          : 3
          Affiliations
          [1 ]Department of Clinical Gene Therapy, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
          [2 ]Department of Geriatric Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
          [3 ]Division of Vascular Medicine and Epigenetics, United Graduate School of Child Development, Osaka University, Suita, Osaka, Japan
          University of Illinois at Chicago, United States Of America
          Author notes

          Competing Interests: Prof. Ryuichi Morishita is a PLOS ONE Editorial Board Member. However, this does not alter the authors' adherence to all the PLOS ONE politics on sharing data and materials.

          Conceived and designed the experiments: FN HN RM. Performed the experiments: FN HN HK MKO MK. Analyzed the data: FN HN MS TM TK. Contributed reagents/materials/analysis tools: TK HR. Wrote the paper: FN HN RM.

          Article
          PONE-D-12-31152
          10.1371/journal.pone.0060493
          3609829
          23544146

          This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

          Page count
          Pages: 9
          Funding
          This work was partially supported by Grant-in-Aid for Scientific Research from Japan Society for the Promotion of Science (JSPS) and Adaptive and Seamless Technology Transfer Program (A-step) by from Japan Science and Technology Agency (JST). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
          Categories
          Research Article
          Medicine
          Cardiovascular
          Angina
          Aortic Diseases
          Atherosclerosis
          Cardiovascular Pharmacology
          Coronary Artery Disease
          Heart Failure
          Hypertension
          Vascular Biology
          Clinical Immunology
          Immunity
          Vaccination
          Immune Response

          Uncategorized

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