{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T16:35:15Z","timestamp":1775666115836,"version":"3.50.1"},"reference-count":50,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2024,12,10]],"date-time":"2024-12-10T00:00:00Z","timestamp":1733788800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["CA175112"],"award-info":[{"award-number":["CA175112"]}]},{"name":"NIH","award":["CA118113"],"award-info":[{"award-number":["CA118113"]}]},{"name":"NIH","award":["CA178730"],"award-info":[{"award-number":["CA178730"]}]},{"name":"NIH","award":["# S10OD027045"],"award-info":[{"award-number":["# S10OD027045"]}]},{"name":"NIH","award":["CA175112"],"award-info":[{"award-number":["CA175112"]}]},{"name":"NIH","award":["CA118113"],"award-info":[{"award-number":["CA118113"]}]},{"name":"NIH","award":["CA178730"],"award-info":[{"award-number":["CA178730"]}]},{"name":"NIH","award":["# S10OD027045"],"award-info":[{"award-number":["# S10OD027045"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Substantial loss of cardiomyocytes during heart attacks and onset of other cardiovascular diseases is a major cause of mortality. Preservation of cardiomyocytes during cardiac injury would be the most effective strategy to manage these diseases in clinic. However, there is no effective treatment strategy that is able to prevent cardiomyocyte loss. We demonstrate here that the systemic administration of a recombinant PKM2 mutant (G415R) preserves cardiomyocytes and reduces cardiac fibrosis during myocardial infarction. G415R preserves cardiomyocytes by protecting the cardiomyocytes from dying and by promoting cardiomyocyte proliferation. Preservation of cardiomyocytes by extracellular PKM2 (EcPKM2) reduces cardiac fibrosis because of the decreased activation of cardiac fibroblasts. Our experiments show that EcPKM2 (G415R) exerts its action by interacting with integrin avb3 on cardiomyocytes. EcPKM2(G415R) activates the integrin\u2013FAK\u2013PI3K signaling axis, which subsequently suppresses PTEN expression and consequently regulates cardiomyocyte apoptosis resistance and proliferation under hypoxia and oxidative stress conditions. Our studies uncover an important cardiomyocyte protection mechanism. More importantly, the activity\/action of EcPKM2 (G415R) in preserving cardiomyocyte suggesting a possible therapeutic strategy and target for the treatment of heart attacks and other cardiovascular diseases.<\/jats:p>","DOI":"10.3390\/ijms252413246","type":"journal-article","created":{"date-parts":[[2024,12,10]],"date-time":"2024-12-10T08:40:10Z","timestamp":1733820010000},"page":"13246","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Extracellular PKM2 Preserves Cardiomyocytes and Reduces Cardiac Fibrosis During Myocardial Infarction"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1873-1675","authenticated-orcid":false,"given":"Yang","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Biology, Georgia State University, Atlanta, GA 30303, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biology, Georgia State University, Atlanta, GA 30303, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zongxiang","family":"Gui","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Georgia State University, Atlanta, GA 30303, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erhe","family":"Gao","sequence":"additional","affiliation":[{"name":"Center for Translational Medicine, Temple University, Philadelphia, PA 19140, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Biology, Georgia State University, Atlanta, GA 30303, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2310-7658","authenticated-orcid":false,"given":"Jenny","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Georgia State University, Atlanta, GA 30303, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Khan","family":"Hekmatyar","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Georgia State University, Atlanta, GA 30303, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Falguni","family":"Mishra","sequence":"additional","affiliation":[{"name":"Department of Biology, Georgia State University, Atlanta, GA 30303, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-1744-2265","authenticated-orcid":false,"given":"Payton","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Biology, Georgia State University, Atlanta, GA 30303, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2460-1631","authenticated-orcid":false,"given":"Zhiren","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Biology, Georgia State University, Atlanta, GA 30303, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1177\/1074248411407769","article-title":"How and when do myocytes die during ischemia and reperfusion: The late phase","volume":"16","author":"Baines","year":"2011","journal-title":"J. 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