Back to Search Start Over

Stamp2 Protects From Maladaptive Structural Remodeling and Systolic Dysfunction in Post-Ischemic Hearts by Attenuating Neutrophil Activation

Authors :
Martin Mollenhauer
Senai Bokredenghel
Simon Geißen
Anna Klinke
Tobias Morstadt
Merve Torun
Sabrina Strauch
Wibke Schumacher
Martina Maass
Jürgen Konradi
Vera B. M. Peters
Eva Berghausen
Marius Vantler
Stephan Rosenkranz
Dennis Mehrkens
Simon Braumann
Felix Nettersheim
Alexander Hof
Sakine Simsekyilmaz
Holger Winkels
Volker Rudolph
Stephan Baldus
Matti Adam
Henrik ten Freyhaus
Source :
Frontiers in Immunology, Frontiers in Immunology, Vol 12 (2021)
Publication Year :
2021

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.

Details

ISSN :
16643224
Volume :
12
Database :
OpenAIRE
Journal :
Frontiers in immunology
Accession number :
edsair.doi.dedup.....5f49077f58fabea21c333487c670a90b