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Indeed, while neonatal mammals can regenerate cardiac tissue mainly through cardiomyocyte proliferation, this ability is lost shortly after birth, resulting in the adult heart\u2019s inability to regenerate after injury effectively. In adult mammals, the adverse cardiac remodelling, which compensates for the loss of cardiac cells, impairs cardiac function due to the non-contractile nature of fibrotic tissue. Moreover, the neovascularisation after MI is inadequate to restore blood flow to the infarcted myocardium. This review aims to synthesise the most recent insights into the molecular and cellular players involved in endogenous myocardial and vascular regeneration, facilitating the identification of mechanisms that could be targeted to trigger cardiac regeneration, reduce fibrosis, and improve functional recovery post-MI. Reprogramming adult cardiomyocytes to regain their proliferative potential, along with the modulation of target cells responsible for neovascularisation, represents promising therapeutic strategies. An updated overview of endogenous mechanisms that regulate both myocardial and coronary vasculature regeneration\u2014including stem and progenitor cells, growth factors, cell cycle regulators, and key signalling pathways\u2014could help identify new critical intervention points for therapeutic applications.<\/jats:p>","DOI":"10.3390\/ijms252111747","type":"journal-article","created":{"date-parts":[[2024,11,1]],"date-time":"2024-11-01T04:59:54Z","timestamp":1730437194000},"page":"11747","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Recent Insights into Endogenous Mammalian Cardiac Regeneration Post-Myocardial Infarction"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8662-9525","authenticated-orcid":false,"given":"Erika","family":"Fiorino","sequence":"first","affiliation":[{"name":"Department of Clinical and Biological Sciences, University of Turin, Regione Gonzole 10, 10043 Orbassano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5741-5774","authenticated-orcid":false,"given":"Daniela","family":"Rossin","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biological Sciences, University of Turin, Regione Gonzole 10, 10043 Orbassano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Vanni","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biological Sciences, University of Turin, Regione Gonzole 10, 10043 Orbassano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Aubry","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biological Sciences, University of Turin, Regione Gonzole 10, 10043 Orbassano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7957-3925","authenticated-orcid":false,"given":"Claudia","family":"Giachino","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biological Sciences, University of Turin, Regione Gonzole 10, 10043 Orbassano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8673-9409","authenticated-orcid":false,"given":"Raffaella","family":"Rastaldo","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biological Sciences, University of Turin, Regione Gonzole 10, 10043 Orbassano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2361","DOI":"10.1016\/j.jacc.2022.11.005","article-title":"The Global Burden of Cardiovascular Diseases and Risk","volume":"80","author":"Vaduganathan","year":"2022","journal-title":"J. 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