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Mortality at 6 wk was higher in TG mice (24% in WT vs. 44% in TG, P &lt; 0.05) driven by a significantly higher incidence of cardiac rupture during the first week post-MI, despite comparable infarct size and LV dysfunction and dilatation. Calpain activation post-MI was blunted in TG myocardium. In TG mice, inflammatory cell infiltration and activation were reduced in the infarct zone (IZ), particularly affecting M2 macrophages and CD4<jats:sup>+<\/jats:sup> T cells, which are crucial for scar healing. To elucidate the role of calpastatin overexpression in macrophages, we stimulated peritoneal macrophages obtained from TG and WT mice in vitro with IL-4, yielding an abrogated M2 polarization in TG but not in WT cells. Lymphopenic Rag1<jats:sup>\u2212\/\u2212<\/jats:sup> mice receiving TG splenocytes before MI demonstrated decreased T-cell recruitment and M2 macrophage activation in the IZ day 5 after MI compared with those receiving WT splenocytes. Calpastatin overexpression prevented the activation of the calpain system after MI. It also impaired scar healing, promoted LV rupture, and increased mortality. Defective scar formation was associated with blunted CD4<jats:sup>+<\/jats:sup> T-cell and M2-macrophage recruitment. <\/jats:p>","DOI":"10.1152\/ajpheart.00594.2015","type":"journal-article","created":{"date-parts":[[2015,10,9]],"date-time":"2015-10-09T22:58:44Z","timestamp":1444431524000},"page":"H1883-H1893","source":"Crossref","is-referenced-by-count":25,"title":["Calpastatin overexpression impairs postinfarct scar healing in mice by compromising reparative immune cell recruitment and activation"],"prefix":"10.1152","volume":"309","author":[{"given":"Feng","family":"Wan","sequence":"first","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U955, Universit\u00e9 Paris-Est Creteil, Cr\u00e9teil, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel","family":"Letavernier","sequence":"additional","affiliation":[{"name":"Department of Physiology, Assistance Publique-H\u00f4pitaux de Paris (AP-HP), Tenon Hospital, 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