title: Long-Term Reduction of High Blood Pressure by Angiotensin II DNA Vaccine in Spontaneously Hypertensive Rats.
abstract: 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.
authors.affiliation: From the Division of Vascular Medicine and Epigenetics, Osaka University United Graduate School of Child Development, Suita, Osaka, Japan (H.K., H.N., M.K.O., M.S., H.K.); Departments of Clinical Gene Therapy (F.N., M.K., T.K., R.M.) and Geriatric Medicine and Nephrology (F.N., H.R.), Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Koriyama
authors.affiliation: From the Division of Vascular Medicine and Epigenetics, Osaka University United Graduate School of Child Development, Suita, Osaka, Japan (H.K., H.N., M.K.O., M.S., H.K.); Departments of Clinical Gene Therapy (F.N., M.K., T.K., R.M.) and Geriatric Medicine and Nephrology (F.N., H.R.), Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Nakagami
authors.affiliation: From the Division of Vascular Medicine and Epigenetics, Osaka University United Graduate School of Child Development, Suita, Osaka, Japan (H.K., H.N., M.K.O., M.S., H.K.); Departments of Clinical Gene Therapy (F.N., M.K., T.K., R.M.) and Geriatric Medicine and Nephrology (F.N., H.R.), Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Futoshi
authors.initials: F
authors.lastname: Nakagami
authors.affiliation: From the Division of Vascular Medicine and Epigenetics, Osaka University United Graduate School of Child Development, Suita, Osaka, Japan (H.K., H.N., M.K.O., M.S., H.K.); Departments of Clinical Gene Therapy (F.N., M.K., T.K., R.M.) and Geriatric Medicine and Nephrology (F.N., H.R.), Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Mariana Kiomy
authors.initials: MK
authors.lastname: Osako
authors.affiliation: From the Division of Vascular Medicine and Epigenetics, Osaka University United Graduate School of Child Development, Suita, Osaka, Japan (H.K., H.N., M.K.O., M.S., H.K.); Departments of Clinical Gene Therapy (F.N., M.K., T.K., R.M.) and Geriatric Medicine and Nephrology (F.N., H.R.), Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Kyutoku
authors.affiliation: From the Division of Vascular Medicine and Epigenetics, Osaka University United Graduate School of Child Development, Suita, Osaka, Japan (H.K., H.N., M.K.O., M.S., H.K.); Departments of Clinical Gene Therapy (F.N., M.K., T.K., R.M.) and Geriatric Medicine and Nephrology (F.N., H.R.), Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Munehisa
authors.initials: M
authors.lastname: Shimamura
authors.affiliation: From the Division of Vascular Medicine and Epigenetics, Osaka University United Graduate School of Child Development, Suita, Osaka, Japan (H.K., H.N., M.K.O., M.S., H.K.); Departments of Clinical Gene Therapy (F.N., M.K., T.K., R.M.) and Geriatric Medicine and Nephrology (F.N., H.R.), Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Kurinami
authors.affiliation: From the Division of Vascular Medicine and Epigenetics, Osaka University United Graduate School of Child Development, Suita, Osaka, Japan (H.K., H.N., M.K.O., M.S., H.K.); Departments of Clinical Gene Therapy (F.N., M.K., T.K., R.M.) and Geriatric Medicine and Nephrology (F.N., H.R.), Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Katsuya
authors.affiliation: From the Division of Vascular Medicine and Epigenetics, Osaka University United Graduate School of Child Development, Suita, Osaka, Japan (H.K., H.N., M.K.O., M.S., H.K.); Departments of Clinical Gene Therapy (F.N., M.K., T.K., R.M.) and Geriatric Medicine and Nephrology (F.N., H.R.), Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Rakugi
authors.affiliation: From the Division of Vascular Medicine and Epigenetics, Osaka University United Graduate School of Child Development, Suita, Osaka, Japan (H.K., H.N., M.K.O., M.S., H.K.); Departments of Clinical Gene Therapy (F.N., M.K., T.K., R.M.) and Geriatric Medicine and Nephrology (F.N., H.R.), Osaka University Graduate School of Medicine, Suita, Osaka, Japan. morishita@cgt.med.osaka-u.ac.jp nakagami@gts.med.osaka-u.ac.jp.
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Morishita
mesh_terms: D000804:Angiotensin II / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D000818:Animals; D017951:Antigen Presentation; D001011:Aorta / Q000473:pathology; D004353:Drug Evaluation, Preclinical; D005813:Genes, Synthetic; D006367:HeLa Cells; D006512:Hepatitis B Core Antigens / Q000276:immunology; D006801:Humans; D006973:Hypertension / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D007114:Immunization; D016056:Immunodominant Epitopes / Q000235:genetics / Q000276:immunology; D016233:Immunotherapy, Active; D007518:Isoantibodies / Q000096:biosynthesis; D007668:Kidney / Q000473:pathology; D008099:Liver / Q000473:pathology; D008213:Lymphocyte Activation; D008297:Male; D009206:Myocardium / Q000473:pathology; D051381:Rats; D011918:Rats, Inbred SHR; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D019444:Vaccines, DNA / Q000627:therapeutic use*
chemical_list: D006512:Hepatitis B Core Antigens; D016056:Immunodominant Epitopes; D007518:Isoantibodies; D011993:Recombinant Fusion Proteins; D019444:Vaccines, DNA; D000804:Angiotensin II
keywords: allergy and immunology; angiotensin II; genetic therapy; hypertension; vaccine therapy