{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T02:40:57Z","timestamp":1785465657785,"version":"3.56.0"},"reference-count":38,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Cardiovascular Interventions"],"published-print":{"date-parts":[[2016,1]]},"abstract":"<jats:sec>\n            <jats:title>Background\u2014<\/jats:title>\n            <jats:p>Acute coronary syndrome is the leading cause of mortality worldwide. However, treatment of acute coronary occlusion inevitably results in ischemia-reperfusion injury. Circulating natural IgM has been shown to play a significant role in mouse models of ischemia-reperfusion injury. A highly conserved self-antigen, nonmuscle myosin heavy chain II, has been identified as a target of pathogenic IgM. We hypothesized that a monoclonal antibody (m21G6) directed against nonmuscle myosin heavy chain II may inhibit IgM binding and reduce injury in a preclinical model of myocardial infarction. Thus, our objective was to evaluate the efficacy of intravenous m21G6 treatment in limiting infarct expansion, troponin release, and left ventricular dysfunction in a swine myocardial infarction model.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results\u2014<\/jats:title>\n            <jats:p>\n              Massachusetts General Hospital miniature swine underwent occlusion of the midleft anterior descending coronary artery for 60 minutes, followed by 1 hour, 5-day, or 21-day reperfusion. Specificity and localization of m21G6 to injured myocardium were confirmed using fluorescently labeled m21G6. Treatment with m21G6 before reperfusion resulted in a 49% reduction in infarct size (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.005) and a 61% reduction in troponin-T levels (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.05) in comparison with saline controls at 5-day reperfusion. Furthermore, m21G6-treated animals recovered 85.4% of their baseline left ventricular function as measured by 2-dimensional transthoracic echocardiography in contrast to 67.1% in controls at 21-day reperfusion (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.05).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>Treatment with m21G6 significantly reduced infarct size and troponin-T release, and led to marked preservation of cardiac function in our study. Overall, these findings suggest that pathogenic IgM blockade represents a valid therapeutic strategy in mitigating myocardial ischemia-reperfusion injury.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circinterventions.115.002547","type":"journal-article","created":{"date-parts":[[2015,12,16]],"date-time":"2015-12-16T03:38:54Z","timestamp":1450237134000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":6,"title":["Natural IgM Blockade Limits Infarct Expansion and Left Ventricular Dysfunction in a Swine Myocardial Infarct Model"],"prefix":"10.1161","volume":"9","author":[{"given":"Smita","family":"Sihag","sequence":"first","affiliation":[{"name":"From the Transplantation Biology Research Center, Massachusetts General Hospital, Charlestown (S.S., J.D.G., J.C.M., D.H.S., J.S.A.); Cardiac Surgery Research Laboratory, Massachusetts General Hospital, Boston, (J.L.G., J.B., J.S.A.); DecImmune Therapeutics, Cambridge, MA (M.S.H., E.M.A., F.S., R.J.P., W.N.); Program in Cellular and Molecular Medicine, Boston Children\u2019s Hospital, MA (M.C.C.); Department of Pediatrics, Harvard Medical School, Boston, MA (M.C.C.); and Division of Cardiovascular..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael S.","family":"Haas","sequence":"additional","affiliation":[{"name":"From the Transplantation Biology Research Center, Massachusetts General Hospital, Charlestown (S.S., J.D.G., J.C.M., D.H.S., J.S.A.); Cardiac Surgery Research Laboratory, Massachusetts General Hospital, Boston, (J.L.G., J.B., J.S.A.); DecImmune Therapeutics, Cambridge, MA (M.S.H., E.M.A., F.S., R.J.P., W.N.); Program in Cellular and Molecular Medicine, Boston Children\u2019s Hospital, MA (M.C.C.); Department of Pediatrics, Harvard Medical School, Boston, MA (M.C.C.); and Division of Cardiovascular..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen M.","family":"Kim","sequence":"additional","affiliation":[{"name":"From the Transplantation Biology Research Center, Massachusetts General Hospital, Charlestown (S.S., J.D.G., J.C.M., D.H.S., J.S.A.); Cardiac Surgery Research Laboratory, Massachusetts General Hospital, Boston, (J.L.G., J.B., J.S.A.); DecImmune Therapeutics, Cambridge, MA (M.S.H., E.M.A., F.S., R.J.P., W.N.); Program in Cellular and Molecular Medicine, Boston Children\u2019s Hospital, MA (M.C.C.); Department of Pediatrics, Harvard Medical School, Boston, MA (M.C.C.); and Division of Cardiovascular..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Luis","family":"Guerrero","sequence":"additional","affiliation":[{"name":"From the Transplantation Biology Research Center, Massachusetts General Hospital, Charlestown (S.S., J.D.G., J.C.M., D.H.S., J.S.A.); Cardiac Surgery Research Laboratory, Massachusetts General Hospital, Boston, (J.L.G., J.B., J.S.A.); DecImmune Therapeutics, Cambridge, MA (M.S.H., E.M.A., F.S., R.J.P., W.N.); Program in Cellular and Molecular Medicine, Boston Children\u2019s Hospital, MA (M.C.C.); Department of Pediatrics, Harvard Medical School, Boston, MA (M.C.C.); and Division of Cardiovascular..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Beaudoin","sequence":"additional","affiliation":[{"name":"From the Transplantation Biology Research Center, Massachusetts General Hospital, Charlestown (S.S., J.D.G., J.C.M., D.H.S., J.S.A.); Cardiac Surgery Research Laboratory, Massachusetts General Hospital, Boston, (J.L.G., J.B., J.S.A.); DecImmune Therapeutics, Cambridge, MA (M.S.H., E.M.A., F.S., R.J.P., W.N.); Program in Cellular and Molecular Medicine, Boston Children\u2019s Hospital, MA (M.C.C.); Department of Pediatrics, Harvard Medical School, Boston, MA (M.C.C.); and Division of Cardiovascular..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth M.","family":"Alicot","sequence":"additional","affiliation":[{"name":"From the Transplantation Biology Research Center, Massachusetts General Hospital, Charlestown (S.S., J.D.G., J.C.M., D.H.S., J.S.A.); Cardiac Surgery Research Laboratory, Massachusetts General Hospital, Boston, (J.L.G., J.B., J.S.A.); DecImmune Therapeutics, Cambridge, MA (M.S.H., E.M.A., F.S., R.J.P., W.N.); Program in Cellular and Molecular Medicine, Boston Children\u2019s Hospital, MA (M.C.C.); Department of Pediatrics, Harvard Medical School, Boston, MA (M.C.C.); and Division of Cardiovascular..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franziska","family":"Schuerpf","sequence":"additional","affiliation":[{"name":"From the Transplantation Biology Research Center, Massachusetts General Hospital, Charlestown (S.S., J.D.G., J.C.M., D.H.S., J.S.A.); Cardiac Surgery Research Laboratory, Massachusetts General Hospital, Boston, (J.L.G., J.B., J.S.A.); DecImmune Therapeutics, Cambridge, MA (M.S.H., E.M.A., F.S., R.J.P., W.N.); Program in Cellular and Molecular Medicine, Boston Children\u2019s Hospital, MA (M.C.C.); Department of Pediatrics, Harvard Medical School, Boston, MA (M.C.C.); and Division of Cardiovascular..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James D.","family":"Gottschall","sequence":"additional","affiliation":[{"name":"From the Transplantation Biology Research Center, Massachusetts General Hospital, Charlestown (S.S., J.D.G., J.C.M., D.H.S., J.S.A.); Cardiac Surgery Research Laboratory, Massachusetts General Hospital, Boston, (J.L.G., J.B., J.S.A.); DecImmune Therapeutics, Cambridge, MA (M.S.H., E.M.A., F.S., R.J.P., W.N.); Program in Cellular and Molecular Medicine, Boston Children\u2019s Hospital, MA (M.C.C.); Department of Pediatrics, Harvard Medical School, Boston, MA (M.C.C.); and Division of Cardiovascular..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robyn J.","family":"Puro","sequence":"additional","affiliation":[{"name":"From the Transplantation Biology Research Center, Massachusetts General Hospital, Charlestown (S.S., J.D.G., J.C.M., D.H.S., J.S.A.); Cardiac Surgery Research Laboratory, Massachusetts General Hospital, Boston, (J.L.G., J.B., J.S.A.); DecImmune Therapeutics, Cambridge, MA (M.S.H., E.M.A., F.S., R.J.P., W.N.); Program in Cellular and Molecular Medicine, Boston Children\u2019s Hospital, MA (M.C.C.); Department of Pediatrics, Harvard Medical School, Boston, MA (M.C.C.); and Division of Cardiovascular..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joren C.","family":"Madsen","sequence":"additional","affiliation":[{"name":"From the Transplantation Biology Research Center, Massachusetts General Hospital, Charlestown (S.S., J.D.G., J.C.M., D.H.S., J.S.A.); Cardiac Surgery Research Laboratory, Massachusetts General Hospital, Boston, (J.L.G., J.B., J.S.A.); DecImmune Therapeutics, Cambridge, MA (M.S.H., E.M.A., F.S., R.J.P., W.N.); Program in Cellular and Molecular Medicine, Boston Children\u2019s Hospital, MA (M.C.C.); Department of Pediatrics, Harvard Medical School, Boston, MA (M.C.C.); and Division of Cardiovascular..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David H.","family":"Sachs","sequence":"additional","affiliation":[{"name":"From the Transplantation Biology Research Center, Massachusetts General Hospital, Charlestown (S.S., J.D.G., J.C.M., D.H.S., J.S.A.); 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