{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T06:55:18Z","timestamp":1790060118114,"version":"4.0.1"},"reference-count":56,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"13","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2024,3,26]]},"abstract":"<jats:sec>\n            <jats:title>BACKGROUND:<\/jats:title>\n            <jats:p>The adult mammalian heart is incapable of regeneration, whereas a transient regenerative capacity is maintained in the neonatal heart, primarily through the proliferation of preexisting cardiomyocytes. Neonatal heart regeneration after myocardial injury is accompanied by an expansion of cardiac fibroblasts and compositional changes in the extracellular matrix. Whether and how these changes influence cardiomyocyte proliferation and heart regeneration remains to be investigated.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS:<\/jats:title>\n            <jats:p>\n              We used apical resection and myocardial infarction surgical models in neonatal and adult mice to investigate extracellular matrix components involved in heart regeneration after injury. Single-cell RNA sequencing and liquid chromatography\u2013mass spectrometry analyses were used for versican identification. Cardiac fibroblast\u2013specific\n              <jats:italic toggle=\"yes\">Vcan<\/jats:italic>\n              deletion was achieved using the mouse strains\n              <jats:italic toggle=\"yes\">Col1a2-2A-CreER<\/jats:italic>\n              and\n              <jats:italic toggle=\"yes\">\n                Vcan\n                <jats:sup>fl\/fl<\/jats:sup>\n              <\/jats:italic>\n              . Molecular signaling pathways related to the effects of versican were assessed through Western blot, immunostaining, and quantitative reverse transcription polymerase chain reaction. Cardiac fibrosis and heart function were evaluated by Masson trichrome staining and echocardiography, respectively.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS:<\/jats:title>\n            <jats:p>\n              Versican, a cardiac fibroblast\u2013derived extracellular matrix component, was upregulated after neonatal myocardial injury and promoted cardiomyocyte proliferation. Conditional knockout of\n              <jats:italic toggle=\"yes\">Vcan<\/jats:italic>\n              in cardiac fibroblasts decreased cardiomyocyte proliferation and impaired neonatal heart regeneration. In adult mice, intramyocardial injection of versican after myocardial infarction enhanced cardiomyocyte proliferation, reduced fibrosis, and improved cardiac function. Furthermore, versican augmented the proliferation of human induced pluripotent stem cell\u2013derived cardiomyocytes. Mechanistically, versican activated integrin \u03b21 and downstream signaling molecules, including ERK1\/2 and Akt, thereby promoting cardiomyocyte proliferation and cardiac repair.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSIONS:<\/jats:title>\n            <jats:p>Our study identifies versican as a cardiac fibroblast\u2013derived pro-proliferative proteoglycan and clarifies the role of versican in promoting adult cardiac repair. These findings highlight its potential as a therapeutic factor for ischemic heart diseases.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circulationaha.123.066298","type":"journal-article","created":{"date-parts":[[2023,10,27]],"date-time":"2023-10-27T05:01:56Z","timestamp":1698382916000},"page":"1004-1015","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":114,"title":["Versican Promotes Cardiomyocyte Proliferation and Cardiac Repair"],"prefix":"10.1161","volume":"149","author":[{"given":"Jie","family":"Feng","sequence":"first","affiliation":[{"name":"State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (J.F., Y.D.L., H.T.L., J.L., J.M., H.L., Y.H.L., K.F.D., W.H.S., B.L., L.H.L., S.S.H., Y.N.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yandong","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (J.F., Y.D.L., H.T.L., J.L., J.M., H.L., Y.H.L., K.F.D., W.H.S., B.L., L.H.L., S.S.H., Y.N.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Tribology, Tsinghua University, Beijing, China (Y.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1252-3613","authenticated-orcid":true,"given":"Qianqian","family":"Yin","sequence":"additional","affiliation":[{"name":"Institute of Medical Innovation and Research, Peking University Third Hospital, Peking University, Beijing, China 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