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Endogenous vascular repair processes are deployed following injury but are poorly understood. We sought to determine whether developmental mechanisms of coronary vessel formation are intrinsically reactivated in the adult mouse after MI. Using pulse-chase genetic lineage tracing, we establish that de novo vessel formation constitutes a substantial component of the neovascular response, with apparent cellular contributions from the endocardium and coronary sinus. The adult heart reverts to its former hypertrabeculated state and repeats the process of compaction, which may facilitate endocardium-derived neovascularization. The capacity for angiogenic sprouting of the coronary sinus vein, the adult derivative of the sinus venosus, may also reflect its embryonic origin. The quiescent epicardium is reactivated and, while direct cellular contribution to new vessels is minimal, it supports the directional expansion of the neovessel network toward the infarcted myocardium. Thymosin \u03b24, a peptide with roles in vascular development, was required for endocardial compaction, epicardial vessel expansion, and smooth muscle cell recruitment. Insight into pathways that regulate endogenous vascular repair, drawing on comparisons with development, may reveal novel targets for therapeutically enhancing neovascularization.<\/jats:p>","DOI":"10.1172\/jci.insight.96800","type":"journal-article","created":{"date-parts":[[2017,11,15]],"date-time":"2017-11-15T11:00:38Z","timestamp":1510743638000},"source":"Crossref","is-referenced-by-count":72,"title":["Recapitulation of developmental mechanisms to revascularize the ischemic heart"],"prefix":"10.1172","volume":"2","author":[{"given":"Karina N.","family":"Dub\u00e9","sequence":"first","affiliation":[{"name":"UCL Institute of Child Health, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tonia M.","family":"Thomas","sequence":"additional","affiliation":[{"name":"British Heart Foundation Centre of Regenerative Medicine, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United 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