{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T03:13:56Z","timestamp":1792120436603,"version":"4.4.0"},"reference-count":53,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"16","license":[{"start":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T00:00:00Z","timestamp":1776729600000},"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"],"published-print":{"date-parts":[[2026,4,21]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>During myocardial infarction (MI), M1-like macrophages exacerbate myocardial injury by excessively secreting inflammatory cytokines. Therefore, modulating the activity of M1-like macrophages may represent a novel therapeutic strategy for MI. PRMTs (protein arginine methyltransferases) primarily regulate protein function via asymmetric dimethylation, but PRMT9 does so through symmetric dimethylation. However, its role in cardiovascular diseases has yet to be established. In this study, we investigated the role of PRMT9 in macrophage polarization in the context of MI and explored its therapeutic effect for MI.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>\n                      The correlation between PRMT9 in monocytes\/macrophages and MI was investigated using the MI dataset GSE166780. Peripheral blood mononuclear cells were obtained from healthy individuals and patients with MI and analyzed to assess PRMT9 expression. We elucidated the functional role of PRMT9 in MI using macrophage-specific\n                      <jats:italic toggle=\"yes\">Prmt9<\/jats:italic>\n                      knockout mice and macrophage-specific overexpression adeno-associated virus vectors. We explored the underlying mechanisms through flow cytometry, transcriptome analysis, immunoprecipitation\/mass spectrometry analysis, and functional experiments.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>We discovered that PRMT9 was highly expressed in murine and human peripheral blood mononuclear cells in the early stages of MI. PRMT9 deficiency enhanced M1-like polarization and exacerbated cardiac damage in murine models of MI. Conversely, PRMT9 overexpression in macrophages reduced infarct size, accelerated inflammation resolution, and improved cardiac function after MI. Our findings established that PRMT9-catalyzed methylation played an important role in STAT1 (signal transducer and activator of transcription 1)\u2013mediated macrophage polarization. Mechanistically, PRMT9 directly binds to STAT1 and facilitates its symmetric dimethylation at R588 and R736. Further analysis revealed that PRMT9-mediated symmetric dimethylation facilitated STAT1 ubiquitination, which promoted STAT1 recognition by SQSTM1\/p62 (sequestosome-1) and NDP52\/CALCOCO2 (nuclear dot protein 52), facilitating STAT1-selective autophagic degradation and suppressing excessive M1-like macrophage responses. Moreover, we demonstrated that the STAT1 inhibitor fludarabine, a clinically used chemotherapeutic agent, mitigated the exacerbation of post-MI myocardial injury induced by PRMT9 deletion in macrophages.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>This study discovered a novel PRMT9-driven symmetric dimethylation of STAT1, resulting in its ubiquitination and lysosomal degradation, which suppresses the proinflammatory polarization of macrophages and mitigates myocardial damage following MI.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circulationaha.125.076101","type":"journal-article","created":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T10:00:12Z","timestamp":1770804012000},"page":"1233-1254","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":8,"title":["Macrophage PRMT9 Ameliorates Acute Myocardial Infarction by Promoting Symmetric Dimethylation and Degradation of STAT1"],"prefix":"10.1161","volume":"153","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9711-4199","authenticated-orcid":true,"given":"Xuemei","family":"Bai","sequence":"first","affiliation":[{"name":"Key Laboratory of Infection, Immunity and Prevention of Shandong Province and Key Laboratory for Experimental Teratology of Ministry of Education, Shandong University, Jinan, Shandong 250012, P.R. China (X.B., J.Y., N.D., N.C., M. Zhou, J.Z., X.L., Z.H., B.L., C.G.)."},{"name":"Department of Immunology, Shandong University, Jinan, Shandong 250012, P.R. China (X.B., J.Y., N.D., N.C., M. Zhou, J.Z., X.L., Z.H., B.L., C.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-6118-9601","authenticated-orcid":true,"given":"Ruiqing","family":"Ren","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Innovation and Transformation of Luobing Theory; Key Laboratory of Cardiovascular Remodeling and Function Research of MOE, NHC, CAMS and Shandong Province; Department of Cardiology, Qilu Hospital of Shandong University, Jinan, China (R.R., L.Y., M. Zhang)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7964-4295","authenticated-orcid":true,"given":"Jiahua","family":"Yuan","sequence":"additional","affiliation":[{"name":"Key Laboratory of Infection, Immunity and Prevention of Shandong Province and Key Laboratory for Experimental Teratology of Ministry of Education, Shandong University, Jinan, Shandong 250012, P.R. China (X.B., J.Y., N.D., N.C., M. Zhou, J.Z., X.L., Z.H., B.L., C.G.)."},{"name":"Department of Immunology, Shandong University, Jinan, Shandong 250012, P.R. China (X.B., J.Y., N.D., N.C., M. Zhou, J.Z., X.L., Z.H., B.L., C.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3012-6993","authenticated-orcid":true,"given":"Liwen","family":"Yu","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Innovation and Transformation of Luobing Theory; Key Laboratory of Cardiovascular Remodeling and Function Research of MOE, NHC, CAMS and Shandong Province; Department of Cardiology, Qilu Hospital of Shandong University, Jinan, China (R.R., L.Y., M. Zhang)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Dong","sequence":"additional","affiliation":[{"name":"Key Laboratory of Infection, Immunity and Prevention of Shandong Province and Key Laboratory for Experimental Teratology of Ministry of Education, Shandong University, Jinan, Shandong 250012, P.R. China (X.B., J.Y., N.D., N.C., M. Zhou, J.Z., X.L., Z.H., B.L., C.G.)."},{"name":"Department of Immunology, Shandong University, Jinan, Shandong 250012, P.R. China (X.B., J.Y., N.D., N.C., M. Zhou, J.Z., X.L., Z.H., B.L., C.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Cao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Infection, Immunity and Prevention of Shandong Province and Key Laboratory for Experimental Teratology of Ministry of Education, Shandong University, Jinan, Shandong 250012, P.R. China (X.B., J.Y., N.D., N.C., M. Zhou, J.Z., X.L., Z.H., B.L., C.G.)."},{"name":"Department of Immunology, Shandong University, Jinan, Shandong 250012, P.R. China (X.B., J.Y., N.D., N.C., M. Zhou, J.Z., X.L., Z.H., B.L., C.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Zhou","sequence":"additional","affiliation":[{"name":"Key Laboratory of Infection, Immunity and Prevention of Shandong Province and Key Laboratory for Experimental Teratology of Ministry of Education, Shandong University, Jinan, Shandong 250012, P.R. China (X.B., J.Y., N.D., N.C., M. Zhou, J.Z., X.L., Z.H., B.L., C.G.)."},{"name":"Department of Immunology, Shandong University, Jinan, Shandong 250012, P.R. China (X.B., J.Y., N.D., N.C., M. Zhou, J.Z., X.L., Z.H., B.L., C.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JiaJia","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Infection, Immunity and Prevention of Shandong Province and Key Laboratory for Experimental Teratology of Ministry of Education, Shandong University, Jinan, Shandong 250012, P.R. China (X.B., J.Y., N.D., N.C., M. Zhou, J.Z., X.L., Z.H., B.L., C.G.)."},{"name":"Department of Immunology, Shandong University, Jinan, Shandong 250012, P.R. China (X.B., J.Y., N.D., N.C., M. Zhou, J.Z., X.L., Z.H., B.L., C.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxiao","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Infection, Immunity and Prevention of Shandong Province and Key Laboratory for Experimental Teratology of Ministry of Education, Shandong University, Jinan, Shandong 250012, P.R. China (X.B., J.Y., N.D., N.C., M. Zhou, J.Z., X.L., Z.H., B.L., C.G.)."},{"name":"Department of Immunology, Shandong University, Jinan, Shandong 250012, P.R. China (X.B., J.Y., N.D., N.C., M. 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