Frontiers in Immunology (Oct 2021)
Stamp2 Protects From Maladaptive Structural Remodeling and Systolic Dysfunction in Post-Ischemic Hearts by Attenuating Neutrophil Activation
- Martin Mollenhauer,
- Martin Mollenhauer,
- Martin Mollenhauer,
- Senai Bokredenghel,
- Senai Bokredenghel,
- Senai Bokredenghel,
- Simon Geißen,
- Simon Geißen,
- Simon Geißen,
- Anna Klinke,
- Anna Klinke,
- Anna Klinke,
- Tobias Morstadt,
- Merve Torun,
- Merve Torun,
- Merve Torun,
- Sabrina Strauch,
- Wibke Schumacher,
- Wibke Schumacher,
- Wibke Schumacher,
- Martina Maass,
- Jürgen Konradi,
- Vera B. M. Peters,
- Vera B. M. Peters,
- Vera B. M. Peters,
- Eva Berghausen,
- Eva Berghausen,
- Eva Berghausen,
- Marius Vantler,
- Marius Vantler,
- Marius Vantler,
- Stephan Rosenkranz,
- Stephan Rosenkranz,
- Stephan Rosenkranz,
- Dennis Mehrkens,
- Dennis Mehrkens,
- Dennis Mehrkens,
- Simon Braumann,
- Simon Braumann,
- Simon Braumann,
- Felix Nettersheim,
- Felix Nettersheim,
- Felix Nettersheim,
- Alexander Hof,
- Alexander Hof,
- Alexander Hof,
- Sakine Simsekyilmaz,
- Sakine Simsekyilmaz,
- Holger Winkels,
- Holger Winkels,
- Holger Winkels,
- Volker Rudolph,
- Volker Rudolph,
- Volker Rudolph,
- Stephan Baldus,
- Stephan Baldus,
- Stephan Baldus,
- Matti Adam,
- Matti Adam,
- Matti Adam,
- Henrik ten Freyhaus,
- Henrik ten Freyhaus,
- Henrik ten Freyhaus
Affiliations
- Martin Mollenhauer
- Department for Experimental Cardiology, Faculty of Medicine, University of Cologne, and Clinic III for Internal Medicine, University Hospital Cologne, Cologne, Germany
- Martin Mollenhauer
- Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany
- Martin Mollenhauer
- Cologne Cardiovascular Research Center (CCRC), University of Cologne, Cologne, Germany
- Senai Bokredenghel
- Department for Experimental Cardiology, Faculty of Medicine, University of Cologne, and Clinic III for Internal Medicine, University Hospital Cologne, Cologne, Germany
- Senai Bokredenghel
- Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany
- Senai Bokredenghel
- Cologne Cardiovascular Research Center (CCRC), University of Cologne, Cologne, Germany
- Simon Geißen
- Department for Experimental Cardiology, Faculty of Medicine, University of Cologne, and Clinic III for Internal Medicine, University Hospital Cologne, Cologne, Germany
- Simon Geißen
- Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany
- Simon Geißen
- Cologne Cardiovascular Research Center (CCRC), University of Cologne, Cologne, Germany
- Anna Klinke
- Department for Experimental Cardiology, Faculty of Medicine, University of Cologne, and Clinic III for Internal Medicine, University Hospital Cologne, Cologne, Germany
- Anna Klinke
- Cologne Cardiovascular Research Center (CCRC), University of Cologne, Cologne, Germany
- Anna Klinke
- Clinic for General and Interventional Cardiology/Angiology, Herz- und Diabeteszentrum Nordrhein-Westfalen, University Hospital Ruhr-Universität Bochum, Bad Oeynhausen, Germany
- Tobias Morstadt
- Department for Experimental Cardiology, Faculty of Medicine, University of Cologne, and Clinic III for Internal Medicine, University Hospital Cologne, Cologne, Germany
- Merve Torun
- Department for Experimental Cardiology, Faculty of Medicine, University of Cologne, and Clinic III for Internal Medicine, University Hospital Cologne, Cologne, Germany
- Merve Torun
- Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany
- Merve Torun
- Cologne Cardiovascular Research Center (CCRC), University of Cologne, Cologne, Germany
- Sabrina Strauch
- Department for Experimental Cardiology, Faculty of Medicine, University of Cologne, and Clinic III for Internal Medicine, University Hospital Cologne, Cologne, Germany
- Wibke Schumacher
- Department for Experimental Cardiology, Faculty of Medicine, University of Cologne, and Clinic III for Internal Medicine, University Hospital Cologne, Cologne, Germany
- Wibke Schumacher
- Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany
- Wibke Schumacher
- Cologne Cardiovascular Research Center (CCRC), University of Cologne, Cologne, Germany
- Martina Maass
- Department for Experimental Cardiology, Faculty of Medicine, University of Cologne, and Clinic III for Internal Medicine, University Hospital Cologne, Cologne, Germany
- Jürgen Konradi
- Department for Experimental Cardiology, Faculty of Medicine, University of Cologne, and Clinic III for Internal Medicine, University Hospital Cologne, Cologne, Germany
- Vera B. M. Peters
- Department for Experimental Cardiology, Faculty of Medicine, University of Cologne, and Clinic III for Internal Medicine, University Hospital Cologne, Cologne, Germany
- Vera B. M. Peters
- Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany
- Vera B. M. Peters
- Cologne Cardiovascular Research Center (CCRC), University of Cologne, Cologne, Germany
- Eva Berghausen
- Department for Experimental Cardiology, Faculty of Medicine, University of Cologne, and Clinic III for Internal Medicine, University Hospital Cologne, Cologne, Germany
- Eva Berghausen
- Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany
- Eva Berghausen
- Cologne Cardiovascular Research Center (CCRC), University of Cologne, Cologne, Germany
- Marius Vantler
- Department for Experimental Cardiology, Faculty of Medicine, University of Cologne, and Clinic III for Internal Medicine, University Hospital Cologne, Cologne, Germany
- Marius Vantler
- Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany
- Marius Vantler
- Cologne Cardiovascular Research Center (CCRC), University of Cologne, Cologne, Germany
- Stephan Rosenkranz
- Department for Experimental Cardiology, Faculty of Medicine, University of Cologne, and Clinic III for Internal Medicine, University Hospital Cologne, Cologne, Germany
- Stephan Rosenkranz
- Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany
- Stephan Rosenkranz
- Cologne Cardiovascular Research Center (CCRC), University of Cologne, Cologne, Germany
- Dennis Mehrkens
- Department for Experimental Cardiology, Faculty of Medicine, University of Cologne, and Clinic III for Internal Medicine, University Hospital Cologne, Cologne, Germany
- Dennis Mehrkens
- Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany
- Dennis Mehrkens
- Cologne Cardiovascular Research Center (CCRC), University of Cologne, Cologne, Germany
- Simon Braumann
- Department for Experimental Cardiology, Faculty of Medicine, University of Cologne, and Clinic III for Internal Medicine, University Hospital Cologne, Cologne, Germany
- Simon Braumann
- Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany
- Simon Braumann
- Cologne Cardiovascular Research Center (CCRC), University of Cologne, Cologne, Germany
- Felix Nettersheim
- Department for Experimental Cardiology, Faculty of Medicine, University of Cologne, and Clinic III for Internal Medicine, University Hospital Cologne, Cologne, Germany
- Felix Nettersheim
- Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany
- Felix Nettersheim
- Cologne Cardiovascular Research Center (CCRC), University of Cologne, Cologne, Germany
- Alexander Hof
- Department for Experimental Cardiology, Faculty of Medicine, University of Cologne, and Clinic III for Internal Medicine, University Hospital Cologne, Cologne, Germany
- Alexander Hof
- Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany
- Alexander Hof
- Cologne Cardiovascular Research Center (CCRC), University of Cologne, Cologne, Germany
- Sakine Simsekyilmaz
- Department for Experimental Cardiology, Faculty of Medicine, University of Cologne, and Clinic III for Internal Medicine, University Hospital Cologne, Cologne, Germany
- Sakine Simsekyilmaz
- Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany
- Holger Winkels
- Department for Experimental Cardiology, Faculty of Medicine, University of Cologne, and Clinic III for Internal Medicine, University Hospital Cologne, Cologne, Germany
- Holger Winkels
- Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany
- Holger Winkels
- Cologne Cardiovascular Research Center (CCRC), University of Cologne, Cologne, Germany
- Volker Rudolph
- Department for Experimental Cardiology, Faculty of Medicine, University of Cologne, and Clinic III for Internal Medicine, University Hospital Cologne, Cologne, Germany
- Volker Rudolph
- Cologne Cardiovascular Research Center (CCRC), University of Cologne, Cologne, Germany
- Volker Rudolph
- Clinic for General and Interventional Cardiology/Angiology, Herz- und Diabeteszentrum Nordrhein-Westfalen, University Hospital Ruhr-Universität Bochum, Bad Oeynhausen, Germany
- Stephan Baldus
- Department for Experimental Cardiology, Faculty of Medicine, University of Cologne, and Clinic III for Internal Medicine, University Hospital Cologne, Cologne, Germany
- Stephan Baldus
- Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany
- Stephan Baldus
- Cologne Cardiovascular Research Center (CCRC), University of Cologne, Cologne, Germany
- Matti Adam
- Department for Experimental Cardiology, Faculty of Medicine, University of Cologne, and Clinic III for Internal Medicine, University Hospital Cologne, Cologne, Germany
- Matti Adam
- Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany
- Matti Adam
- Cologne Cardiovascular Research Center (CCRC), University of Cologne, Cologne, Germany
- Henrik ten Freyhaus
- Department for Experimental Cardiology, Faculty of Medicine, University of Cologne, and Clinic III for Internal Medicine, University Hospital Cologne, Cologne, Germany
- Henrik ten Freyhaus
- Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany
- Henrik ten Freyhaus
- Cologne Cardiovascular Research Center (CCRC), University of Cologne, Cologne, Germany
- DOI
- https://doi.org/10.3389/fimmu.2021.701721
- Journal volume & issue
-
Vol. 12
Abstract
The six-transmembrane protein of prostate 2 (Stamp2) acts as an anti-inflammatory protein in macrophages by protecting from overt inflammatory signaling and Stamp2 deficiency accelerates atherosclerosis in mice. Herein, we describe an unexpected role of Stamp2 in polymorphonuclear neutrophils (PMN) and characterize Stamp2’s protective effects in myocardial ischemic injury. In a murine model of ischemia and reperfusion (I/R), echocardiography and histological analyses revealed a pronounced impairment of cardiac function in hearts of Stamp2-deficient- (Stamp2-/-) mice as compared to wild-type (WT) animals. This difference was driven by aggravated cardiac fibrosis, as augmented fibroblast-to-myofibroblast transdifferentiation was observed which was mediated by activation of the redox-sensitive p38 mitogen-activated protein kinase (p38 MAPK). Furthermore, we observed increased production of reactive oxygen species (ROS) in Stamp2-/- hearts after I/R, which is the likely cause for p38 MAPK activation. Although myocardial macrophage numbers were not affected by Stamp2 deficiency after I/R, augmented myocardial infiltration by polymorphonuclear neutrophils (PMN) was observed, which coincided with enhanced myeloperoxidase (MPO) plasma levels. Primary PMN isolated from Stamp2-/- animals exhibited a proinflammatory phenotype characterized by enhanced nuclear factor (NF)-κB activity and MPO secretion. To prove the critical role of PMN for the observed phenotype after I/R, antibody-mediated PMN depletion was performed in Stamp2-/- mice which reduced deterioration of LV function and adverse structural remodeling to WT levels. These data indicate a novel role of Stamp2 as an anti-inflammatory regulator of PMN and fibroblast-to-myofibroblast transdifferentiation in myocardial I/R injury.
Keywords
- six-transmembrane protein of prostate 2
- Stamp2
- Steap4
- myocardial infarction
- ischemia and reperfusion damage
- left ventricular dysfunction
