Background/Aims: Data from mouse experiments indicate that plasminogen activator inhibitor-1 (PAI-1) is cardioprotective by repressing cardiac fibrosis through TGF-β and plasminogen mediated pathways. In addition it is linked to the recruitment and polarization of non-classical M2 macrophages in cancer. Here, we investigated the expression of cardiac PAI-1 in human dilated cardiomyopathy (DCM) and inflammatory dilated cardiomyopathy (DCMi) and its effect on myofibroblast activation and macrophage polarization.

Methods: We retrospectively analyzed endomyocardial biopsies (EMBs) of patients with DCM (n=27) or DCMi (n=149) for PAI-1 expression, number of activated myofibroblasts and M1/M2 macrophages.

Results: Patients with severe DCMi (DCMi-high, CD3⁺ lymphocytes > 30 cells/mm²) had significantly increased PAI-1 levels compared to DCM and low grade DCMi patients (DCMi-low, CD3⁺ lymphocytes = 14 - 30 cells/mm²) (15.5 ± 0.4 % vs. 1.0 ± 0.1 % and 4.0 ± 0.1 %, p ≤ 0.001). Elevated PAI-1 expression in DCMi-high subjects was accompanied by a reduced number of alpha smooth muscle actin (α-SMA) positive myofibroblasts and an increased number of CD16⁺ CD68⁺ M2 macrophages, indicating anti-fibrogenic and M2 macrophage-favoring properties of PAI-1 in inflammatory cardiomyopathies.

Conclusion: Our findings give evidence that elevated expression of PAI-1 in EMBs of subjects with high-grade DCMi suppresses myofibroblast activation and promotes M2 macrophage polarization. Thus, PAI-1 could serve as a potential prognostic biomarker and as a possible therapeutic target in inflammatory cardiomyopathies.