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In addition it is known to be involved in the recruitment and polarization of monocytes\/macrophages towards a M2 phenotype in cancer. Here, we investigated the expression of PAI-1 in human\u00a0dilated cardiomyopathy (DCM) and inflammatory\u00a0dilated cardiomyopathy (DCMi) and its effect on cardiac fibrosis and macrophage polarization. We retrospectively analyzed endomyocardial biopsies (EMBs) of patients with DCM or DCMi for PAI-1 expression by immunohistochemistry. Furthermore, EMBs were evaluated for the content of fibrotic tissue, number of activated myofibroblasts, TGF-\u03b2 expression, as well as for M1 and M2 macrophages. Patients with high-grade DCMi (DCMi-high, CD3<jats:sup>+<\/jats:sup> lymphocytes\u2009&gt;\u200930 cells\/mm<jats:sup>2<\/jats:sup>) had significantly increased PAI-1 levels compared to DCM and low-grade DCMi patients (DCMi-low, CD3<jats:sup>+<\/jats:sup> lymphocytes\u2009=\u200914\u201330 cells\/mm<jats:sup>2<\/jats:sup>) (15.5\u2009\u00b1\u20090.4% vs. 1.0\u2009\u00b1\u20090.1% and 4.0\u2009\u00b1\u20090.1%, <jats:italic>p<\/jats:italic>\u2009\u2264\u20090.001). Elevated PAI-1 expression in DCMi-high subjects was associated with a diminished degree of cardiac fibrosis, decreased levels of TGF-\u03b2 and reduced number of myofibroblasts. In addition, DCMi-high patients revealed an increased proportion of non-classical M2 macrophages towards classical M1 macrophages, indicating M2 macrophage-favoring properties of PAI-1 in inflammatory cardiomyopathies. Our findings give evidence that elevated expression of cardiac PAI-1 in subjects with high-grade DCMi suppresses fibrosis by inhibiting TGF-\u03b2 and myofibroblast activation. Moreover, our data indicate that PAI-1 is involved in the polarization of M2 macrophages in the heart. Thus, PAI-1 could serve as a potential prognostic biomarker and as a possible therapeutic target in inflammatory cardiomyopathies.<\/jats:p>","DOI":"10.1007\/s00395-020-00840-w","type":"journal-article","created":{"date-parts":[[2021,1,12]],"date-time":"2021-01-12T04:09:16Z","timestamp":1610424556000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":65,"title":["Plasminogen activator inhibitor-1 reduces cardiac fibrosis and promotes M2 macrophage polarization in inflammatory cardiomyopathy"],"prefix":"10.1007","volume":"116","author":[{"given":"Christian","family":"Baumeier","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felicitas","family":"Escher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ganna","family":"Aleshcheva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heiko","family":"Pietsch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heinz-Peter","family":"Schultheiss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,1,11]]},"reference":[{"key":"840_CR1","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1016\/s0046-8177(87)80363-5","volume":"18","author":"HT Aretz","year":"1987","unstructured":"Aretz HT (1987) Myocarditis: the Dallas criteria. 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