@article{0e722950d5ea4c4a9ea10712f3fdaecf,
title = "Neutrophils Modulate Fibroblast Function and Promote Healing and Scar Formation after Murine Myocardial Infarction",
abstract = "Aim: Recruitment of neutrophils to the heart following acute myocardial infarction (MI) initiates inflammation and contributes to adverse post-infarct left ventricular (LV) remodeling. However, therapeutic inhibition of neutrophil recruitment into the infarct zone has not been beneficial in MI patients, suggesting a possible dual role for neutrophils in inflammation and repair following MI. Here, we investigate the effect of neutrophils on cardiac fibroblast function following MI. Methods and Results: We found that co-incubating neutrophils with isolated cardiac fibroblasts enhanced the production of provisional extracellular matrix proteins and reduced collagen synthesis when compared to control or co-incubation with mononuclear cells. Furthermore, we showed that neutrophils are required to induce the transient up-regulation of transforming growth factor (TGF)-ss 1 expression in fibroblasts, a key requirement for terminating the pro-inflammatory phase and allowing the reparatory phase to form a mature scar after MI. Conclusion: Neutrophils are essential for both initiation and termination of inflammatory events that control and modulate the healing process after MI. Therefore, one should exercise caution when testing therapeutic strategies to inhibit neutrophil recruitment into the infarct zone in MI patients.",
keywords = "myocardial infarction, inflammation, neutrophils, fibroblasts, extracellular matrix formation, scar formation, EXTRACELLULAR-MATRIX, VENTRICULAR-FUNCTION, AT(2) RECEPTORS, INHIBITION, EXPRESSION, AT(1)",
author = "Adelina Curaj and David Schumacher and Mihaela Rusu and Mareike Staudt and Xiaofeng Li and Sakine Simsekyilmaz and Vera Jankowski and Joachim Jankowski and Dumitrascu, {Andreea Ramona} and Hausenloy, {Derek J.} and Alexander Schuh and Liehn, {Elisa A.}",
note = "Funding Information: Funding: This study was supported by the Interdisciplinary Centre for Clinical Research IZKF Aachen (junior research group to E.A.L.) within the faculty of Medicine at RWTH Aachen University. The authors J.J. and J.V. were supported by grants from the German Research Funding Organization (DFG SFB/TRR219). D.S. was supported by the Clinician Scientist program of the Faculty of Medicine of the RWTH Aachen University. D.J.H. was supported by the British Heart Foundation (FS/10/039/28270), the National Institute for Health Research University College London Hospitals Biomedical Research Centre, Duke‐National University Singapore Medical School, Singapore Ministry of Health National Medical Research Council under its Clinician Scientist‐Senior Investigator scheme (NMRC/CSA‐SI/0011/2017) and Collaborative Centre Grant scheme (NMRC/CGAug16C006), and the Singapore Ministry of Education Academic Research Fund Tier 2 (MOE2016‐ T2‐2‐021). This article is based upon work from COST Action EU‐CARDIOPROTECTION CA16225 supported by COST (European Cooperation in Science and Technology). Funding Information: This study was supported by the Interdisciplinary Centre for Clinical Research IZKF Aachen (junior research group to E.A.L.) within the faculty of Medicine at RWTH Aachen University. The authors J.J. and J.V. were supported by grants from the German Research Funding Organization (DFG SFB/TRR219). D.S. was supported by the Clinician Scientist program of the Faculty of Medicine of the RWTH Aachen University. D.J.H. was supported by the British Heart Foundation (FS/10/039/28270), the National Institute for Health Research University College London Hospitals Biomedical Research Centre, Duke?National University Singapore Medical School, Singapore Ministry of Health National Medical Research Council under its Clinician Scientist?Senior Investigator scheme (NMRC/CSA?SI/0011/2017) and Collaborative Centre Grant scheme (NMRC/CGAug16C006), and the Singapore Ministry of Education Academic Research Fund Tier 2 (MOE 2016? T2?2?021). This article is based upon work from COST Action EU?CARDIOPROTECTION CA16225 supported by COST (European Cooperation in Science and Technology). Publisher Copyright: {\textcopyright} 2020 by the authors. Licensee MDPI, Basel, Switzerland.",
year = "2020",
month = may,
doi = "10.3390/ijms21103685",
language = "English",
volume = "21",
journal = "International journal of molecular sciences",
issn = "1661-6596",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "10",
}