{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T03:03:19Z","timestamp":1792724599698,"version":"4.5.0"},"reference-count":33,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"20","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2022,5,17]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Cardiac resident macrophages are self-maintaining and originate from embryonic hematopoiesis. After myocardial infarction, cardiac resident macrophages are responsible for the efficient clearance and degradation of apoptotic cardiomyocytes (efferocytosis). This process is required for inflammation resolution and tissue repair; however, the underlying molecular mechanisms remain unknown. Therefore, we aimed to identify the mechanisms of the continued clearance and degradation of phagolysosomal cargo by cardiac resident macrophages during myocardial infarction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      Multiple transgenic mice such as Lgmn\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      , Lgmn\n                      <jats:sup>F\/F<\/jats:sup>\n                      ; LysM\n                      <jats:sup>Cre<\/jats:sup>\n                      , Lgmn\n                      <jats:sup>F\/F<\/jats:sup>\n                      ; Cx3cr1\n                      <jats:sup>CreER<\/jats:sup>\n                      , Lgmn\n                      <jats:sup>F\/F<\/jats:sup>\n                      ; Lyve\n                      <jats:sup>Cre<\/jats:sup>\n                      , and cardiac macrophage Lgmn overexpression by adenovirus gene transfer were used to determine the functional significance of Lgmn in myocardial infarction. Immune cell filtration and inflammation were examined by flow cytometry and quantitative real-time polymerase chain reaction. Moreover, legumain (Lgmn) expression was analyzed by immunohistochemistry and quantitative real-time polymerase chain reaction in the cardiac tissues of patients with ischemic cardiomyopathy and healthy control subjects.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      We identified\n                      <jats:italic>Lgmn<\/jats:italic>\n                      as a gene specifically expressed by cardiac resident macrophages. Lgmn deficiency resulted in a considerable exacerbation in cardiac function, accompanied by the accumulation of apoptotic cardiomyocytes and a reduced index of in vivo efferocytosis in the border area. It also led to decreased cytosolic calcium attributable to defective intracellular calcium mobilization. Furthermore, the formation of LC3-II\u2013dependent phagosome around secondary-encountered apoptotic cardiomyocytes was disabled. In addition, Lgmn deficiency increased infiltration of MHC-II\n                      <jats:sup>high<\/jats:sup>\n                      CCR2\n                      <jats:sup>+<\/jats:sup>\n                      macrophages and the enhanced recruitment of MHC-II\n                      <jats:sup>low<\/jats:sup>\n                      CCR2\n                      <jats:sup>+<\/jats:sup>\n                      monocytes with downregulation of the anti-inflammatory mediators, interleukin-10, and transforming growth factor-\u03b2 and upregulationof the proinflammatory mediators interleukin-1\u03b2, tumor necrosis factor-\u03b1, interleukin-6, and interferon-\u03b3.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Our results directly link efferocytosis to wound healing in the heart and identify Lgmn as a significant link between acute inflammation resolution and organ function.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circulationaha.121.057549","type":"journal-article","created":{"date-parts":[[2022,4,18]],"date-time":"2022-04-18T05:00:14Z","timestamp":1650258014000},"page":"1542-1556","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":247,"title":["Cardiac Resident Macrophage-Derived Legumain Improves Cardiac Repair by Promoting Clearance and Degradation of Apoptotic Cardiomyocytes After Myocardial Infarction"],"prefix":"10.1161","volume":"145","author":[{"given":"Daile","family":"Jia","sequence":"first","affiliation":[{"name":"Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, China (D.J., P.B., J.L., A.S., J.G.)."},{"name":"Key Laboratory of Viral Heart Diseases, National Health Commission, Shanghai, China (D.J., S.C., P.B., J.L., A.S., J.G.)."},{"name":"Key Laboratory of Viral Heart Diseases, Chinese Academy of Medical Sciences, Shanghai, China (D.J., S.C., P.B., J.L., A.S., J.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siqin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, China (D.J., P.B., J.L., A.S., J.G.)."},{"name":"Key Laboratory of Viral Heart Diseases, National Health Commission, Shanghai, China (D.J., S.C., P.B., J.L., A.S., J.G.)."},{"name":"Key Laboratory of Viral Heart Diseases, Chinese Academy of Medical Sciences, Shanghai, China (D.J., S.C., P.B., J.L., A.S., J.G.)."},{"name":"Institutes of Biomedical Sciences, Fudan University, Shanghai, China (S.C., A.S., J.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7812-2495","authenticated-orcid":true,"given":"Peiyuan","family":"Bai","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, China (D.J., P.B., J.L., A.S., J.G.)."},{"name":"Key Laboratory of Viral Heart Diseases, National Health Commission, Shanghai, China (D.J., S.C., P.B., J.L., A.S., J.G.)."},{"name":"Key Laboratory of Viral Heart Diseases, Chinese Academy of Medical Sciences, Shanghai, China (D.J., S.C., P.B., J.L., A.S., J.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chentao","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, Zhejiang Provincial People\u2019s Hospital, People\u2019s Hospital of Hangzhou Medical College, China (C.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, China (D.J., P.B., J.L., A.S., J.G.)."},{"name":"Key Laboratory of Viral Heart Diseases, National Health Commission, Shanghai, China (D.J., S.C., P.B., J.L., A.S., J.G.)."},{"name":"Key Laboratory of Viral Heart Diseases, Chinese Academy of Medical Sciences, Shanghai, China (D.J., S.C., P.B., J.L., A.S., J.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1488-0937","authenticated-orcid":true,"given":"Aijun","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, China (D.J., P.B., J.L., A.S., J.G.)."},{"name":"Key Laboratory of Viral Heart Diseases, National Health Commission, Shanghai, China (D.J., S.C., P.B., J.L., A.S., J.G.)."},{"name":"Key Laboratory of Viral Heart Diseases, Chinese Academy of Medical Sciences, Shanghai, China (D.J., S.C., P.B., J.L., A.S., J.G.)."},{"name":"Institutes of Biomedical Sciences, Fudan University, Shanghai, China (S.C., A.S., 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