{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T12:01:10Z","timestamp":1792670470626,"version":"4.5.0"},"reference-count":31,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"24","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2018,12,11]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>The adult mammalian heart has limited ability to repair itself after injury. Zebrafish, newts, and neonatal mice can regenerate cardiac tissue, largely by cardiac myocyte (CM) proliferation. It is unknown whether hearts of young large mammals can regenerate.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>We examined the regenerative capacity of the pig heart in neonatal animals (ages 2, 3, or 14 days postnatal) after myocardial infarction or sham procedure. Myocardial scar and left ventricular function were determined by cardiac magnetic resonance imaging and echocardiography. Bromodeoxyuridine pulse-chase labeling, histology, immunohistochemistry, and Western blotting were performed to study cell proliferation, sarcomere dynamics, and cytokinesis and to quantify myocardial fibrosis. RNA-sequencing was also performed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>After myocardial infarction, there was early and sustained recovery of cardiac function and wall thickness in the absence of fibrosis in 2-day-old pigs. In contrast, older animals developed full-thickness myocardial scarring, thinned walls, and did not recover function. Genome-wide analyses of the infarct zone revealed a strong transcriptional signature of fibrosis in 14-day-old animals that was absent in 2-day-old pigs, which instead had enrichment for cytokinesis genes. In regenerating hearts of the younger animals, up to 10% of CMs in the border zone of the myocardial infarction showed evidence of DNA replication that was associated with markers of myocyte division and sarcomere disassembly.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Hearts of large mammals have regenerative capacity, likely driven by cardiac myocyte division, but this potential is lost immediately after birth.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circulationaha.117.031542","type":"journal-article","created":{"date-parts":[[2018,7,20]],"date-time":"2018-07-20T05:26:51Z","timestamp":1532064411000},"page":"2798-2808","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":255,"title":["Early Regenerative Capacity in the Porcine Heart"],"prefix":"10.1161","volume":"138","author":[{"given":"Lei","family":"Ye","sequence":"first","affiliation":[{"name":"National Heart Research Institute Singapore, National Heart Centre Singapore (L.Y., S.J.L., C.X.W., L.P.S., S.H.T., G.Z.T., C.J.P., R.S.T., S.A.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"D\u2019Agostino","sequence":"additional","affiliation":[{"name":"Programme in Cardiovascular &amp; Metabolic Disorders, Duke-National University of Singapore (G.D., S.A.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sze Jie","family":"Loo","sequence":"additional","affiliation":[{"name":"National Heart Research Institute Singapore, National Heart Centre Singapore (L.Y., S.J.L., C.X.W., L.P.S., S.H.T., G.Z.T., C.J.P., R.S.T., S.A.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen Xu","family":"Wang","sequence":"additional","affiliation":[{"name":"National Heart Research Institute Singapore, National Heart Centre Singapore (L.Y., S.J.L., C.X.W., L.P.S., S.H.T., G.Z.T., C.J.P., R.S.T., S.A.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li Ping","family":"Su","sequence":"additional","affiliation":[{"name":"National Heart Research Institute Singapore, National Heart Centre Singapore (L.Y., S.J.L., C.X.W., L.P.S., S.H.T., G.Z.T., C.J.P., R.S.T., S.A.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shi Hua","family":"Tan","sequence":"additional","affiliation":[{"name":"National Heart Research Institute Singapore, National Heart Centre Singapore (L.Y., S.J.L., C.X.W., L.P.S., S.H.T., G.Z.T., C.J.P., R.S.T., S.A.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gui Zhen","family":"Tee","sequence":"additional","affiliation":[{"name":"National Heart Research Institute Singapore, National Heart Centre Singapore (L.Y., S.J.L., C.X.W., L.P.S., S.H.T., G.Z.T., C.J.P., R.S.T., S.A.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chee Jian","family":"Pua","sequence":"additional","affiliation":[{"name":"National Heart Research Institute Singapore, National Heart Centre Singapore (L.Y., S.J.L., C.X.W., L.P.S., S.H.T., G.Z.T., C.J.P., R.S.T., S.A.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edgar Macabe","family":"Pena","sequence":"additional","affiliation":[{"name":"SingHealth Experimental Medicine Centre, Singapore Health Services Pte Ltd (E.M.P., R.B.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Redmond Belen","family":"Cheng","sequence":"additional","affiliation":[{"name":"SingHealth Experimental Medicine Centre, Singapore Health Services Pte Ltd (E.M.P., R.B.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Way Cherng","family":"Chen","sequence":"additional","affiliation":[{"name":"Singapore Bioimaging Consortium, A*STAR (W.C.C., D.A., J.L., T.H.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Desiree","family":"Abdurrachim","sequence":"additional","affiliation":[{"name":"Singapore Bioimaging Consortium, A*STAR (W.C.C., D.A., J.L., T.H.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janise","family":"Lalic","sequence":"additional","affiliation":[{"name":"Singapore Bioimaging Consortium, A*STAR (W.C.C., D.A., J.L., T.H.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ru San","family":"Tan","sequence":"additional","affiliation":[{"name":"National Heart Research Institute Singapore, National Heart Centre Singapore (L.Y., S.J.L., C.X.W., L.P.S., S.H.T., G.Z.T., C.J.P., R.S.T., S.A.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teck Hock","family":"Lee","sequence":"additional","affiliation":[{"name":"Singapore Bioimaging Consortium, A*STAR (W.C.C., D.A., J.L., T.H.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JianYi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Alabama at Birmingham (J.Y.Z.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart Alexander","family":"Cook","sequence":"additional","affiliation":[{"name":"National Heart Research Institute Singapore, National Heart Centre Singapore (L.Y., S.J.L., C.X.W., L.P.S., S.H.T., G.Z.T., C.J.P., R.S.T., S.A.C.)."},{"name":"Programme in Cardiovascular &amp; 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