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Cardiovasc Res. 2019 Nov 11. pii: cvz300. doi: 10.1093/cvr/cvz300. [Epub ahead of print]

In peripartum cardiomyopathy Plasminogen Activator Inhibitor-1 is a potential new biomarker with controversial roles.

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Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany.
Department of Cardiology, AB31, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
Nephrology Department, Hannover Medical School, Hannover, Germany.
Institute of Transplant Immunology, IFB-Tx, Hannover Medical School, Hannover, Germany.
Department of Cardiology, Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany.
Department of Physiology, Ruth & Bruce Rappaport Faculty of Medicine, Technion -Israel Institute of Technology, Haifa, Israel.
Cardiovascular Institute and Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Department of Molecular und Translational Therapy strategies (IMTTS), Hannover Medical School, Hannover, Germany.



Peripartum cardiomyopathy (PPCM) is a life-threatening heart disease occurring in previously healthy women. A common pathomechanism in PPCM involves the angiostatic 16kDa-prolactin (16kDa-PRL) fragment, which via NF-κB-mediated upregulation of microRNA-(miR)-146a induces vascular damage and heart failure. We analyze whether the plasminogen-activator-inhibitor-1 (PAI-1) is involved in PPCM pathophysiology.


In healthy age-matched postpartum women (PP-Ctrl, n = 53, left-ventricular-ejection-fraction, LVEF>55%), PAI-1 plasma levels were within the normal range (21±10 ng/ml), but significantly elevated (64±38 ng/ml, p < 0.01) in postpartum PPCM patients at baseline (BL, n = 64, mean LVEF: 23±8%). At 6-months follow-up (FU, n = 23) PAI-1 levels decreased (36±14 ng/ml, p < 0.01 vs BL) and LVEF (49±11%) improved. Increased NT-proBNP and TroponinT did not correlate with PAI-1. C-reactive protein (CRP), interleukin (IL)-6 and IL-1β did not differ between PPCM patients and PP-Ctrl. MiR-146a) was 3.6-fold (p < 0.001) higher in BL-PPCM plasma compared with PP-Ctrl and correlated positively with PAI-1. In BL-PPCM serum, 16kDa-PRL coprecipitated with PAI-1, which was associated with higher (p < 0.05) uPAR-mediated NF-κB activation in endothelial cells compared with PP-Ctrl serum. Cardiac biopsies and dermal fibroblasts from PPCM patients displayed higher PAI-1 mRNA levels (p < 0.05) than healthy controls. In PPCM mice (due to a cardiomyocyte-specific-knockout for STAT3, CKO), cardiac PAI-1 expression was higher than in postpartum wildtype controls whereas a systemic PAI-1-knockout in CKO mice accelerated peripartum cardiac fibrosis, inflammation, heart failure, and mortality.


In PPCM patients, circulating and cardiac PAI-1 expression are upregulated. While circulating PAI-1 may add 16kDa-PRL to induce vascular impairment via the uPAR/NF-κB/miR-146a pathway, experimental data suggest that cardiac PAI-1 expression seems to protect the PPCM heart from fibrosis. Thus, measuring circulating PAI-1 and miR-146a, together with an uPAR/NF-κB-activity assay could be developed into a specific diagnostic marker assay for PPCM, but unrestricted reduction of PAI-1 for therapy may not be advised.



PAI-1; biomarker; heart failure; miR-146a; peripartum cardiomyopathy


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