{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T18:39:16Z","timestamp":1787510356217,"version":"build-2736575974"},"reference-count":54,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2026,1,6]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">Inflammatory responses are crucial in the pathological cardiac remodeling and tissue repair after myocardial infarction (MI). The lymphatic endothelial cells (LECs) significantly influence immune cell clearance and mitigate cardiac inflammation. Chemokines are known to tightly regulate immune cell mobilization within the infarcted heart, affecting both inflammation and remodeling. However, the role of chemokines expressed by LECs in the regulation of cardiac inflammation post MI remains unclear. Our study aimed to investigate whether LEC\u2010expressing CCL2 (C\u2010C motif chemokine ligand 2) regulated post\u2010MI cardiac remodeling and its underlying molecular mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      We generated LEC\u2010conditional\n                      <jats:italic toggle=\"no\">Ccl2<\/jats:italic>\n                      knockout mice and induced acute MI via left anterior descending coronary artery ligation in these mice. Cardiac function was assessed by echocardiography, and post\u2010MI remodeling was evaluated through serial histological analysis. Immunostaining was performed to examine lymphangiogenesis, macrophage infiltration, and macrophage clearance in the myocardium. Additionally, in\u00a0vitro assays were conducted to investigate the role of LEC\u2010derived CCL2 in macrophage chemotaxis and lymphangiogenesis, including analyses of AKT\/ETS1 (E26 oncogene homolog 1) signaling activation and VEGFC (vascular endothelial growth factor C) expression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      Our results showed that the LEC\u2010\n                      <jats:italic toggle=\"no\">Ccl2<\/jats:italic>\n                      deficiency exacerbated cardiac dysfunction and worsened adverse cardiac remodeling after MI. Further immunostaining analysis showed that the loss of CCL2 in LECs impeded post\u2010MI lymphangiogenesis and increased macrophage infiltration in post\u2010MI myocardium and impaired macrophage clearance via afferent cardiac lymphatics. This led to exacerbated inflammatory responses and pathological cardiac remodeling after MI. In\u00a0vitro studies identified that LEC\u2010derived CCL2 not only induced chemotaxis of macrophages but also activated AKT\/ETS1 signaling, enhancing VEGFC expression and promoting lymphangiogenesis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">This study reveals that cardiac LEC\u2010expressing CCL2 tightly controls macrophage trafficking via lymphatic vessels in injured hearts and thus diminishes post\u2010MI inflammatory responses and lessens adverse cardiac remodeling. Our findings suggest that modulating CCL2 signaling in LECs could provide a promising therapeutic target for resolving excessive inflammation and ameliorating adverse cardiac remodeling after MI.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.124.039153","type":"journal-article","created":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T10:46:25Z","timestamp":1765968385000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":5,"title":["Lymphatic Endothelial C\u2010C Motif Chemokine Ligand 2 Enhances Lymphangiogenesis and Lymphatic Clearance of Macrophages Following Myocardial Infarction"],"prefix":"10.1161","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2855-6150","authenticated-orcid":false,"given":"Shengqiong","family":"Deng","sequence":"first","affiliation":[{"name":"Gongli Hospital of Shanghai Pudong New Area","place":["Shanghai, China"]},{"name":"Ningxia Medical 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