{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T01:06:28Z","timestamp":1792631188516,"version":"4.5.0"},"reference-count":52,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2021,3,24]],"date-time":"2021-03-24T00:00:00Z","timestamp":1616544000000},"content-version":"vor","delay-in-days":23,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82030009"],"award-info":[{"award-number":["82030009"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp; Translational Med"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Prolonged pressure overload triggers cardiac hypertrophy and frequently leads to heart failure (HF). Vascular endothelial growth factor\u2010C (VEGF\u2010C) and its receptor VEGFR\u20103 are components of the central pathway for lymphatic vessel growth (also known as lymphangiogenesis), which has crucial functions in the maintenance of tissue fluid balance and myocardial function after ischemic injury. However, the roles of this pathway in the development of cardiac hypertrophy and dysfunction during pressure overload remain largely unknown. Eight\u2010 to 10\u2010week\u2010old male wild\u2010type (WT) mice, VEGFR\u20103 knockdown (VEGFR\u20103\n                    <jats:sup>f\/\u2212<\/jats:sup>\n                    ) mice, and their WT littermates (VEGFR\u20103\n                    <jats:sup>f\/f<\/jats:sup>\n                    ) were subjected to pressure overload induced by transverse aortic constriction (TAC) for 1\u20136\u00a0weeks. We found that cardiac lymphangiogenesis and the protein expression of VEGF\u2010C and VEGFR\u20103 were upregulated in the early stage of cardiac hypertrophy but were markedly reduced in failing hearts. Moreover, TAC for 6\u00a0weeks significantly reduced cardiac lymphangiogenesis by inhibiting activation of VEGFR\u20103\u2010mediated signals (AKT\/ERK1\/2, calcineurin A\/NFATc1\/FOXc2, and CX43), leading to increased cardiac edema, hypertrophy, fibrosis, apoptosis, inflammation, and dysfunction. These effects were further aggravated in VEGFR\u20103\n                    <jats:sup>f\/\u2212<\/jats:sup>\n                    mice and were dose\u2010dependently attenuated by delivery of recombinant VEGF\u2010C\n                    <jats:sub>156S<\/jats:sub>\n                    in WT mice. VEGF\u2010C\n                    <jats:sub>156s<\/jats:sub>\n                    administration also reversed pre\u2010established cardiac dysfunction induced by sustained pressure overload. Thus, these results demonstrate, for the first time, that activation of the VEGF\u2010C\u2010VEGFR\u20103 axis exerts a protective effect during the transition from cardiac hypertrophy to HF and highlight selective stimulation of cardiac lymphangiogenesis as a potential new therapeutic approach for hypertrophic heart diseases.\n                  <\/jats:p>","DOI":"10.1002\/ctm2.374","type":"journal-article","created":{"date-parts":[[2021,3,24]],"date-time":"2021-03-24T10:29:42Z","timestamp":1616581782000},"source":"Crossref","is-referenced-by-count":86,"title":["VEGF\u2010C\/VEGFR\u20103 axis protects against pressure\u2010overload induced cardiac dysfunction through regulation of lymphangiogenesis"],"prefix":"10.1002","volume":"11","author":[{"given":"Qiu\u2010Yue","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Cardiology, Institute of Cardiovascular Diseases First Affiliated Hospital of Dalian Medical University  Dalian 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