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Cardiac repair after MI is finely organized by complex series of procedures involving a robust angiogenic response that begins in the peri-infarcted border area of the infarcted heart, concluding with fibroblast proliferation and scar formation. Efficient neovascularization after MI limits hypertrophied myocytes and scar extent by the reduction in collagen deposition and sustains the improvement in cardiac function. Compelling evidence from animal models and classical in vitro angiogenic approaches demonstrate that a plethora of well-orchestrated signaling pathways involving Notch, Wnt, PI3K, and the modulation of intracellular Ca2+ concentration through ion channels, regulate angiogenesis from existing endothelial cells (ECs) and endothelial progenitor cells (EPCs) in the infarcted heart. Moreover, cardiac repair after MI involves cell-to-cell communication by paracrine\/autocrine signals, mainly through the delivery of extracellular vesicles hosting pro-angiogenic proteins and non-coding RNAs, as microRNAs (miRNAs). This review highlights some general insights into signaling pathways activated under MI, focusing on the role of Ca2+ influx, Notch activated pathway, and miRNAs in EC activation and angiogenesis after MI.<\/jats:p>","DOI":"10.3390\/ijms241512298","type":"journal-article","created":{"date-parts":[[2023,8,1]],"date-time":"2023-08-01T09:06:44Z","timestamp":1690880804000},"page":"12298","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["New Insights into the Reparative Angiogenesis after Myocardial Infarction"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9472-2666","authenticated-orcid":false,"given":"Marta","family":"Mart\u00edn-B\u00f3rnez","sequence":"first","affiliation":[{"name":"Group of Cardiovascular Pathophysiology, Institute of Biomedicine of Seville, University Hospital of Virgen del Roc\u00edo\/University of Seville\/CSIC, Avenida Manuel Siurot s\/n, 41013 Seville, Spain"},{"name":"Department of Medical Physiology and Biophysics, Faculty of Medicine, University of Seville, 41009 Seville, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D\u00e9bora","family":"Falc\u00f3n","sequence":"additional","affiliation":[{"name":"Group of Cardiovascular Pathophysiology, Institute of Biomedicine of Seville, University Hospital of Virgen del Roc\u00edo\/University of Seville\/CSIC, Avenida Manuel Siurot s\/n, 41013 Seville, Spain"},{"name":"Department of Medical Physiology and Biophysics, Faculty of Medicine, University of Seville, 41009 Seville, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5046-9769","authenticated-orcid":false,"given":"Rosario","family":"Morrugares","sequence":"additional","affiliation":[{"name":"Group of Cardiovascular Pathophysiology, Institute of Biomedicine of Seville, University Hospital of Virgen del Roc\u00edo\/University of Seville\/CSIC, Avenida Manuel Siurot s\/n, 41013 Seville, Spain"},{"name":"Department of Medical Physiology and Biophysics, Faculty of Medicine, University of Seville, 41009 Seville, Spain"},{"name":"Department of Cell Biology, Physiology and Immunology, Universidad de C\u00f3rdoba, 14071 C\u00f3rdoba, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geraldine","family":"Siegfried","sequence":"additional","affiliation":[{"name":"RyTME, Bordeaux Institute of Oncology (BRIC)-UMR1312 Inserm, B2 Ouest, All\u00e9e Geoffroy St Hilaire CS50023, 33615 Pessac, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6957-0384","authenticated-orcid":false,"given":"Abdel-Majid","family":"Khatib","sequence":"additional","affiliation":[{"name":"RyTME, Bordeaux Institute of Oncology (BRIC)-UMR1312 Inserm, B2 Ouest, All\u00e9e Geoffroy St Hilaire CS50023, 33615 Pessac, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9749-2325","authenticated-orcid":false,"given":"Juan A.","family":"Rosado","sequence":"additional","affiliation":[{"name":"Cellular Physiology Research Group, Department of Physiology, Institute of Molecular Pathology Biomarkers (IMPB), University of Extremadura, 10003 Caceres, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3219-4201","authenticated-orcid":false,"given":"Isabel","family":"Galeano-Otero","sequence":"additional","affiliation":[{"name":"Group of Cardiovascular Pathophysiology, Institute of Biomedicine of Seville, University Hospital of Virgen del Roc\u00edo\/University of Seville\/CSIC, Avenida Manuel Siurot s\/n, 41013 Seville, Spain"},{"name":"Department of Medical Physiology and Biophysics, Faculty of Medicine, University of Seville, 41009 Seville, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1877-7438","authenticated-orcid":false,"given":"Tarik","family":"Smani","sequence":"additional","affiliation":[{"name":"Group of Cardiovascular Pathophysiology, Institute of Biomedicine of Seville, University Hospital of Virgen del Roc\u00edo\/University of Seville\/CSIC, Avenida Manuel Siurot s\/n, 41013 Seville, Spain"},{"name":"Department of Medical Physiology and Biophysics, Faculty of Medicine, University of Seville, 41009 Seville, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,1]]},"reference":[{"key":"ref_1","unstructured":"Brown, J.C., Gerhardt, T.E., and Kwon, E. 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