{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T05:31:21Z","timestamp":1792042281168,"version":"4.4.0"},"reference-count":44,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","license":[{"start":{"date-parts":[[2025,1,3]],"date-time":"2025-01-03T00:00:00Z","timestamp":1735862400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2025,1,3]]},"abstract":"<jats:sec>\n            <jats:title>BACKGROUND:<\/jats:title>\n            <jats:p>Myofibroblasts are primary cells involved in chronic response-induced cardiac fibrosis. Fibroblast activation protein (FAP) is a relatively specific marker of activated myofibroblasts and a potential target molecule. This study aimed to clarify whether a vaccine targeting FAP could eliminate myofibroblasts in chronic cardiac stress model mice and reduce cardiac fibrosis.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS:<\/jats:title>\n            <jats:p>We coadministered a FAP peptide vaccine with a cytosine-phosphate-guanine (CpG) K3 oligonucleotide adjuvant to male C57\/BL6J mice and confirmed an elevation in the anti-FAP antibody titer. After continuous angiotensin II and phenylephrine administration for 28 days, we evaluated the degree of cardiac fibrosis and the number of myofibroblasts in cardiac tissues.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS:<\/jats:title>\n            <jats:p>\n              We found that cardiac fibrosis was significantly decreased in the FAP-vaccinated mice compared with the angiotensin II and phenylephrine control mice (3.45\u00b11.11% versus 8.62\u00b14.79%;\n              <jats:italic>P<\/jats:italic>\n              =4.59\u00d710\n              <jats:sup>\u22123<\/jats:sup>\n              ) and that the accumulation of FAP-positive cells was also significantly decreased, as indicated by FAP immunohistochemical staining (4077\u00b11746 versus 7327\u00b11741 cells\/mm\n              <jats:sup>2<\/jats:sup>\n              ; FAP vaccine versus angiotensin II and phenylephrine control;\n              <jats:italic>P<\/jats:italic>\n              =6.67\u00d710\n              <jats:sup>\u22123<\/jats:sup>\n              ). No systemic or organ-specific inflammation due to antibody-dependent cell cytotoxicity induced by the FAP vaccine was observed. Although the transient activation of myofibroblasts has an important role in maintaining the structural robustness in the process of tissue repair, the FAP vaccine showed no adverse effects in myocardial infarction and skin injury models.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSIONS:<\/jats:title>\n            <jats:p>Our study demonstrates the FAP vaccine can be a therapeutic tool for cardiac fibrosis.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circresaha.124.325017","type":"journal-article","created":{"date-parts":[[2024,12,4]],"date-time":"2024-12-04T10:02:01Z","timestamp":1733306521000},"page":"26-40","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":27,"title":["A Vaccine Against Fibroblast Activation Protein Improves Murine Cardiac Fibrosis by Preventing the Accumulation of Myofibroblasts"],"prefix":"10.1161","volume":"136","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6830-7063","authenticated-orcid":true,"given":"Shota","family":"Yoshida","sequence":"first","affiliation":[{"name":"Department of Geriatric and General Medicine (S.Y., S.B., H.R.), Osaka University Graduate School of Medicine, Japan."},{"name":"Department of Health Development and Medicine (S.Y., H.H., J.S., S.B., H.N.), Osaka University Graduate School of Medicine, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5722-3764","authenticated-orcid":true,"given":"Hiroki","family":"Hayashi","sequence":"additional","affiliation":[{"name":"Department of Health Development and Medicine (S.Y., H.H., J.S., S.B., H.N.), Osaka University Graduate School of Medicine, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-0347-4010","authenticated-orcid":true,"given":"Takuro","family":"Kawahara","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan (T. Kawahara, S.K., M.K., R.H., T.M.)."},{"name":"Division of Cardiovascular Medicine, Faculty of Medical Sciences, Research Institute of Angiocardiology, Kyushu University, Fukuoka, Japan (T. Kawahara)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7851-216X","authenticated-orcid":true,"given":"Shunsuke","family":"Katsuki","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan (T. Kawahara, S.K., M.K., R.H., T.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-0966-4144","authenticated-orcid":true,"given":"Mitsukuni","family":"Kimura","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan (T. Kawahara, S.K., M.K., R.H., T.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-4503-4570","authenticated-orcid":true,"given":"Rissei","family":"Hino","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan (T. Kawahara, S.K., M.K., R.H., T.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8843-381X","authenticated-orcid":true,"given":"Jiao","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Health Development and Medicine (S.Y., H.H., J.S., S.B., H.N.), Osaka University Graduate School of Medicine, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0129-7219","authenticated-orcid":true,"given":"Ryo","family":"Nakamaru","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Keio University School of Medicine, Tokyo, Japan; Healthcare Quality Assessment, the University of Tokyo, Japan (R.N.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2406-5824","authenticated-orcid":true,"given":"Akiko","family":"Tenma","sequence":"additional","affiliation":[{"name":"FunPep Co, Ltd, Osaka, Japan (A.T., M.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayoshi","family":"Toyoura","sequence":"additional","affiliation":[{"name":"FunPep Co, Ltd, Osaka, Japan (A.T., M.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-7610-8566","authenticated-orcid":true,"given":"Satoshi","family":"Baba","sequence":"additional","affiliation":[{"name":"Department of Geriatric and General Medicine (S.Y., S.B., H.R.), Osaka University Graduate School of Medicine, Japan."},{"name":"Department of Health Development and Medicine (S.Y., H.H., J.S., S.B., H.N.), Osaka University Graduate School of Medicine, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0374-0787","authenticated-orcid":true,"given":"Munehisa","family":"Shimamura","sequence":"additional","affiliation":[{"name":"Department of Gene and Stem Cell Regenerative Therapy (M.S.), Osaka University Graduate School of Medicine, Japan."},{"name":"Department of Neurology (M.S.), Osaka University Graduate School of Medicine, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8892-8828","authenticated-orcid":true,"given":"Tomohiro","family":"Katsuya","sequence":"additional","affiliation":[{"name":"Department of Clinical Gene Therapy (T. 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