Frontiers in Immunology (Apr 2024)
Myeloperoxidase induces monocyte migration and activation after acute myocardial infarction
- Vera B.M. Peters,
- Vera B.M. Peters,
- Friederike Matheis,
- Immanuel Erdmann,
- Harshal N. Nemade,
- Harshal N. Nemade,
- David Muders,
- Martin Toubartz,
- Merve Torun,
- Merve Torun,
- Dennis Mehrkens,
- Dennis Mehrkens,
- Simon Geißen,
- Simon Geißen,
- Felix Sebastian Nettersheim,
- Felix Sebastian Nettersheim,
- Felix Picard,
- Felix Picard,
- Henning Guthoff,
- Henning Guthoff,
- Alexander Hof,
- Alexander Hof,
- Per Arkenberg,
- Per Arkenberg,
- Birgit Arand,
- Anna Klinke,
- Volker Rudolph,
- Hinrich Peter Hansen,
- Hinrich Peter Hansen,
- Daniel Bachurski,
- Daniel Bachurski,
- Matti Adam,
- Matti Adam,
- Friedrich Felix Hoyer,
- Friedrich Felix Hoyer,
- Holger Winkels,
- Holger Winkels,
- Stephan Baldus,
- Stephan Baldus,
- Martin Mollenhauer,
- Martin Mollenhauer
Affiliations
- Vera B.M. Peters
- Heart Center, Department of Cardiology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
- Vera B.M. Peters
- Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany
- Friederike Matheis
- Heart Center, Department of Cardiology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
- Immanuel Erdmann
- Heart Center, Department of Cardiology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
- Harshal N. Nemade
- Heart Center, Department of Cardiology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
- Harshal N. Nemade
- Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany
- David Muders
- Heart Center, Department of Cardiology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
- Martin Toubartz
- Heart Center, Department of Cardiology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
- Merve Torun
- Heart Center, Department of Cardiology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
- Merve Torun
- Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany
- Dennis Mehrkens
- Heart Center, Department of Cardiology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
- Dennis Mehrkens
- Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany
- Simon Geißen
- Heart Center, Department of Cardiology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
- Simon Geißen
- Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany
- Felix Sebastian Nettersheim
- Heart Center, Department of Cardiology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
- Felix Sebastian Nettersheim
- Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany
- Felix Picard
- Heart Center, Department of Cardiology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
- Felix Picard
- Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany
- Henning Guthoff
- Heart Center, Department of Cardiology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
- Henning Guthoff
- Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany
- Alexander Hof
- Heart Center, Department of Cardiology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
- Alexander Hof
- Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany
- Per Arkenberg
- Heart Center, Department of Cardiology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
- Per Arkenberg
- Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany
- Birgit Arand
- Heart Center, Department of Cardiology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
- Anna Klinke
- Clinic for General and Interventional Cardiology/Angiology, Agnes Wittenborg Institute for Translational Cardiovascular Research, Herz- und Diabeteszentrum Nordrhein Westfalen (NRW), University Hospital of the Ruhr-Universität Bochum, Bad Oeynhausen, Germany
- Volker Rudolph
- Clinic for General and Interventional Cardiology/Angiology, Agnes Wittenborg Institute for Translational Cardiovascular Research, Herz- und Diabeteszentrum Nordrhein Westfalen (NRW), University Hospital of the Ruhr-Universität Bochum, Bad Oeynhausen, Germany
- Hinrich Peter Hansen
- Cluster of Excellence on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany
- Hinrich Peter Hansen
- Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
- Daniel Bachurski
- Cluster of Excellence on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany
- Daniel Bachurski
- Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
- Matti Adam
- Heart Center, Department of Cardiology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
- Matti Adam
- Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany
- Friedrich Felix Hoyer
- Heart Center, Department of Cardiology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
- Friedrich Felix Hoyer
- Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany
- Holger Winkels
- Heart Center, Department of Cardiology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
- Holger Winkels
- Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany
- Stephan Baldus
- Heart Center, Department of Cardiology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
- Stephan Baldus
- Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany
- Martin Mollenhauer
- Heart Center, Department of Cardiology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
- Martin Mollenhauer
- Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany
- DOI
- https://doi.org/10.3389/fimmu.2024.1360700
- Journal volume & issue
-
Vol. 15
Abstract
IntroductionMyocardial infarction (MI) is a significant contributor to morbidity and mortality worldwide. Many individuals who survive the acute event continue to experience heart failure (HF), with inflammatory and healing processes post-MI playing a pivotal role. Polymorphonuclear neutrophils (PMN) and monocytes infiltrate the infarcted area, where PMN release high amounts of the heme enzyme myeloperoxidase (MPO). MPO has numerous inflammatory properties and MPO plasma levels are correlated with prognosis and severity of MI. While studies have focused on MPO inhibition and controlling PMN infiltration into the infarcted tissue, less is known on MPO’s role in monocyte function.Methods and resultsHere, we combined human data with mouse and cell studies to examine the role of MPO on monocyte activation and migration. We revealed a correlation between plasma MPO levels and monocyte activation in a patient study. Using a mouse model of MI, we demonstrated that MPO deficiency led to an increase in splenic monocytes and a decrease in cardiac monocytes compared to wildtype mice (WT). In vitro studies further showed that MPO induces monocyte migration, with upregulation of the chemokine receptor CCR2 and upregulation of inflammatory pathways identified as underlying mechanisms.ConclusionTaken together, we identify MPO as a pro-inflammatory mediator of splenic monocyte recruitment and activation post-MI and provide mechanistic insight for novel therapeutic strategies after ischemic injury.
Keywords
