{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T04:47:56Z","timestamp":1793681276364,"version":"4.5.1"},"reference-count":69,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2019,1,4]]},"abstract":"<jats:sec>\n                    <jats:title>\n                      <jats:underline>Rationale:<\/jats:underline>\n                    <\/jats:title>\n                    <jats:p>Cardiac lymphangiogenesis contributes to the reparative process post-myocardial infarction, but the factors and mechanisms regulating it are not well understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>\n                      <jats:underline>Objective:<\/jats:underline>\n                    <\/jats:title>\n                    <jats:p>\n                      To determine if epicardial-secreted factor AM (adrenomedullin;\n                      <jats:italic>Adm<\/jats:italic>\n                      =gene) improves cardiac lymphangiogenesis post-myocardial infarction via lateralization of Cx43 (connexin 43) in cardiac lymphatic vasculature.\n                    <\/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                      Firstly, we identified sex-dependent differences in cardiac lymphatic numbers in uninjured mice using light-sheet microscopy. Using a mouse model of\n                      <jats:italic>Adm<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>hi\/hi<\/jats:italic>\n                      <\/jats:sup>\n                      (\n                      <jats:italic>Adm<\/jats:italic>\n                      overexpression) and permanent left anterior descending ligation to induce myocardial infarction, we investigated cardiac lymphatic structure, growth, and function in injured murine hearts. Overexpression of\n                      <jats:italic>Adm<\/jats:italic>\n                      increased lymphangiogenesis and cardiac function post-myocardial infarction while suppressing cardiac edema and correlated with changes in Cx43 localization. Lymphatic function in response to AM treatment was attenuated in mice with a lymphatic-specific Cx43 deletion. In vitro experiments in cultured human lymphatic endothelial cells identified a novel mechanism to improve gap junction coupling by pharmaceutically targeting Cx43 with verapamil. Finally, we show that connexin protein expression in cardiac lymphatics is conserved between mouse and human.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>\n                      <jats:underline>Conclusions:<\/jats:underline>\n                    <\/jats:title>\n                    <jats:p>AM is an endogenous, epicardial-derived factor that drives reparative cardiac lymphangiogenesis and function via Cx43, and this represents a new therapeutic pathway for improving myocardial edema after injury.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circresaha.118.313835","type":"journal-article","created":{"date-parts":[[2019,1,3]],"date-time":"2019-01-03T14:00:26Z","timestamp":1546524026000},"page":"101-113","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":133,"title":["Adrenomedullin Induces Cardiac Lymphangiogenesis After Myocardial Infarction and Regulates Cardiac Edema Via Connexin 43"],"prefix":"10.1161","volume":"124","author":[{"given":"Claire E.","family":"Trincot","sequence":"first","affiliation":[{"name":"From the Curriculum in Genetics and Molecular Biology (C.E.T., K.M.C.), The University of North Carolina at Chapel Hill"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjing","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology (W.X., H.Z., M.R.K.), The University of North Carolina at Chapel Hill"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology (W.X., H.Z., M.R.K.), The University of North Carolina at Chapel Hill"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Molly R.","family":"Kulikauskas","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology (W.X., H.Z., M.R.K.), The University of North Carolina at Chapel Hill"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas G.","family":"Caranasos","sequence":"additional","affiliation":[{"name":"Division of Cardiothoracic Surgery, Department of Surgery (T.G.C.), The University of North Carolina at Chapel Hill"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian C.","family":"Jensen","sequence":"additional","affiliation":[{"name":"Division of Cardiology (B.C.J.), The University of North Carolina at Chapel Hill"},{"name":"Department of Medicine, School of Medicine (B.C.J.), The University of North Carolina at Chapel Hill"},{"name":"McAllister Heart Institute (B.C.J., K.M.C.), The University of North Carolina at Chapel Hill"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Am\u00e9lie","family":"Sabine","sequence":"additional","affiliation":[{"name":"Department of Oncology, University of Lausanne and Lausanne University Hospital and Ludwig Institute 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