{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T13:18:02Z","timestamp":1793711882483,"version":"4.6.1"},"reference-count":43,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2017,9,29]]},"abstract":"<jats:sec>\n                    <jats:title>\n                      <jats:underline>Rationale:<\/jats:underline>\n                    <\/jats:title>\n                    <jats:p>Clinical benefits of reperfusion after myocardial infarction are offset by maladaptive innate immune cell function, and therapeutic interventions are lacking.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>\n                      <jats:underline>Objective<\/jats:underline>\n                      :\n                    <\/jats:title>\n                    <jats:p>We sought to test the significance of phagocytic clearance by resident and recruited phagocytes after myocardial ischemia reperfusion.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>\n                      <jats:underline>Methods and Results:<\/jats:underline>\n                    <\/jats:title>\n                    <jats:p>\n                      In humans, we discovered that clinical reperfusion after myocardial infarction led to significant elevation of the soluble form of MerTK (myeloid-epithelial-reproductive tyrosine kinase; ie, soluble MER), a critical biomarker of compromised phagocytosis by innate macrophages. In reperfused mice, macrophage\n                      <jats:italic>Mertk<\/jats:italic>\n                      deficiency led to decreased cardiac wound debridement, increased infarct size, and depressed cardiac function, newly implicating MerTK in cardiac repair after myocardial ischemia reperfusion. More notably,\n                      <jats:italic>Mertk(CR<\/jats:italic>\n                      ) mice, which are resistant to cleavage, showed significantly reduced infarct sizes and improved systolic function. In contrast to other cardiac phagocyte subsets, resident cardiac MHCII\n                      <jats:sup>LO<\/jats:sup>\n                      CCR2\n                      <jats:sup>\u2212<\/jats:sup>\n                      (major histocompatibility complex II\/C-C motif chemokine receptor type 2) macrophages expressed higher levels of MerTK and, when exposed to apoptotic cells, secreted proreparative cytokines, including transforming growth factor-\u03b2.\n                      <jats:italic>Mertk<\/jats:italic>\n                      deficiency compromised the accumulation of MHCII\n                      <jats:sup>LO<\/jats:sup>\n                      phagocytes, and this was rescued in\n                      <jats:italic>Mertk(CR<\/jats:italic>\n                      ) mice. Interestingly, blockade of CCR2-dependent monocyte infiltration into the heart reduced soluble MER levels post-ischemia reperfusion.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>\n                      <jats:underline>Conclusions:<\/jats:underline>\n                    <\/jats:title>\n                    <jats:p>\n                      Our data implicate monocyte-induced MerTK cleavage on proreparative MHCII\n                      <jats:sup>LO<\/jats:sup>\n                      cardiac macrophages as a novel contributor and therapeutic target of reperfusion injury.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circresaha.117.311327","type":"journal-article","created":{"date-parts":[[2017,8,29]],"date-time":"2017-08-29T20:50:16Z","timestamp":1504039816000},"page":"930-940","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":242,"title":["MerTK Cleavage on Resident Cardiac Macrophages Compromises Repair After Myocardial Ischemia Reperfusion Injury"],"prefix":"10.1161","volume":"121","author":[{"given":"Matthew","family":"DeBerge","sequence":"first","affiliation":[{"name":"From the Department of Pathology and Feinberg Cardiovascular Research Institute, Feinberg School of Medicine, Northwestern University, Chicago, IL (M.D., X.Y.Y., S.D., S.Z., L.G., S.M., D.P., X.Z., D.C.Le., W.A.M., X.L., E.B.T.); Division of Molecular Medicine at Columbia University, New York (I.T.); and Department of Immunobiology, School of Medicine, Yale University (C.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin Yi","family":"Yeap","sequence":"additional","affiliation":[{"name":"From the Department of Pathology and Feinberg Cardiovascular Research Institute, Feinberg School of Medicine, Northwestern University, Chicago, IL (M.D., X.Y.Y., S.D., S.Z., L.G., S.M., D.P., X.Z., D.C.Le., W.A.M., X.L., E.B.T.); Division of Molecular Medicine at Columbia University, New York (I.T.); and Department of Immunobiology, School of Medicine, Yale University (C.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shirley","family":"Dehn","sequence":"additional","affiliation":[{"name":"From the Department of Pathology and Feinberg Cardiovascular Research Institute, Feinberg School of Medicine, Northwestern University, Chicago, IL (M.D., X.Y.Y., S.D., S.Z., L.G., S.M., D.P., X.Z., D.C.Le., W.A.M., X.L., E.B.T.); Division of Molecular Medicine at Columbia University, New York (I.T.); and Department of Immunobiology, School of Medicine, Yale University (C.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Zhang","sequence":"additional","affiliation":[{"name":"From the Department of Pathology and Feinberg Cardiovascular Research Institute, Feinberg School of Medicine, Northwestern University, Chicago, IL (M.D., X.Y.Y., S.D., S.Z., L.G., S.M., D.P., X.Z., D.C.Le., W.A.M., X.L., E.B.T.); Division of Molecular Medicine at Columbia University, New York (I.T.); and Department of Immunobiology, School of Medicine, Yale University (C.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lubov","family":"Grigoryeva","sequence":"additional","affiliation":[{"name":"From the Department of Pathology and Feinberg Cardiovascular Research Institute, Feinberg School of Medicine, Northwestern University, Chicago, IL (M.D., X.Y.Y., S.D., S.Z., L.G., S.M., D.P., X.Z., D.C.Le., W.A.M., X.L., E.B.T.); Division of Molecular Medicine at Columbia University, New York (I.T.); and Department of Immunobiology, School of Medicine, Yale University (C.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sol","family":"Misener","sequence":"additional","affiliation":[{"name":"From the Department of Pathology and Feinberg Cardiovascular Research Institute, Feinberg School of Medicine, Northwestern University, Chicago, IL (M.D., X.Y.Y., S.D., S.Z., L.G., S.M., D.P., X.Z., D.C.Le., W.A.M., X.L., E.B.T.); Division of Molecular Medicine at Columbia University, New York (I.T.); and Department of Immunobiology, School of Medicine, Yale University (C.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Procissi","sequence":"additional","affiliation":[{"name":"From the Department of Pathology and Feinberg Cardiovascular Research Institute, Feinberg School of Medicine, Northwestern University, Chicago, IL (M.D., X.Y.Y., S.D., S.Z., L.G., S.M., D.P., X.Z., D.C.Le., W.A.M., X.L., E.B.T.); Division of Molecular Medicine at Columbia University, New York (I.T.); and Department of Immunobiology, School of Medicine, Yale University (C.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Zhou","sequence":"additional","affiliation":[{"name":"From the Department of Pathology and Feinberg Cardiovascular Research Institute, Feinberg School of Medicine, Northwestern University, Chicago, IL (M.D., X.Y.Y., S.D., S.Z., L.G., S.M., D.P., X.Z., D.C.Le., W.A.M., X.L., E.B.T.); Division of Molecular Medicine at Columbia University, New York (I.T.); and Department of Immunobiology, School of Medicine, Yale University (C.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel C.","family":"Lee","sequence":"additional","affiliation":[{"name":"From the Department of Pathology and Feinberg Cardiovascular Research Institute, Feinberg School of Medicine, Northwestern University, Chicago, IL (M.D., X.Y.Y., S.D., S.Z., L.G., S.M., D.P., X.Z., D.C.Le., W.A.M., X.L., E.B.T.); Division of Molecular Medicine at Columbia University, New York (I.T.); and Department of Immunobiology, School of Medicine, Yale University (C.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William A.","family":"Muller","sequence":"additional","affiliation":[{"name":"From the Department of Pathology and Feinberg Cardiovascular Research Institute, Feinberg School of Medicine, Northwestern University, Chicago, IL (M.D., X.Y.Y., S.D., S.Z., L.G., S.M., D.P., X.Z., D.C.Le., W.A.M., X.L., E.B.T.); Division of Molecular Medicine at Columbia University, New York (I.T.); and Department of Immunobiology, School of Medicine, Yale University (C.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xunrong","family":"Luo","sequence":"additional","affiliation":[{"name":"From the Department of Pathology and Feinberg Cardiovascular Research Institute, Feinberg School of Medicine, Northwestern University, Chicago, IL (M.D., X.Y.Y., S.D., S.Z., L.G., S.M., D.P., X.Z., D.C.Le., W.A.M., X.L., E.B.T.); Division of Molecular Medicine at Columbia University, New York (I.T.); and Department of Immunobiology, School of Medicine, Yale University (C.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Rothlin","sequence":"additional","affiliation":[{"name":"From the Department of Pathology and Feinberg Cardiovascular Research Institute, Feinberg School of Medicine, Northwestern University, Chicago, IL (M.D., X.Y.Y., S.D., S.Z., L.G., S.M., D.P., X.Z., D.C.Le., W.A.M., X.L., E.B.T.); Division of Molecular Medicine at Columbia University, New York (I.T.); and Department of Immunobiology, School of Medicine, Yale University (C.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ira","family":"Tabas","sequence":"additional","affiliation":[{"name":"From the Department of Pathology and Feinberg Cardiovascular Research Institute, Feinberg School of Medicine, Northwestern University, Chicago, IL 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