The time‐of‐day of myocardial infarction onset affects healing through oscillations in cardiac neutrophil recruitment
Abstract Myocardial infarction (MI) is the leading cause of death in Western countries. Epidemiological studies show acute MI to be more prevalent in the morning and to be associated with a poorer outcome in terms of mortality and recovery. The mechanisms behind this association are not fully unders...
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| Format: | Article |
| Language: | English |
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Springer Nature
2016-05-01
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| Series: | EMBO Molecular Medicine |
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| Online Access: | https://doi.org/10.15252/emmm.201506083 |
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| author | Maximilian J Schloss Michael Horckmans Katrin Nitz Johan Duchene Maik Drechsler Kiril Bidzhekov Christoph Scheiermann Christian Weber Oliver Soehnlein Sabine Steffens |
| author_facet | Maximilian J Schloss Michael Horckmans Katrin Nitz Johan Duchene Maik Drechsler Kiril Bidzhekov Christoph Scheiermann Christian Weber Oliver Soehnlein Sabine Steffens |
| author_sort | Maximilian J Schloss |
| collection | DOAJ |
| description | Abstract Myocardial infarction (MI) is the leading cause of death in Western countries. Epidemiological studies show acute MI to be more prevalent in the morning and to be associated with a poorer outcome in terms of mortality and recovery. The mechanisms behind this association are not fully understood. Here, we report that circadian oscillations of neutrophil recruitment to the heart determine infarct size, healing, and cardiac function after MI. Preferential cardiac neutrophil recruitment during the active phase (Zeitgeber time, ZT13) was paralleled by enhanced myeloid progenitor production, increased circulating numbers of CXCR2hi neutrophils as well as upregulated cardiac adhesion molecule and chemokine expression. MI at ZT13 resulted in significantly higher cardiac neutrophil infiltration compared to ZT5, which was inhibited by CXCR2 antagonism or neutrophil‐specific CXCR2 knockout. Limiting exaggerated neutrophilic inflammation at this time point significantly reduced the infarct size and improved cardiac function. |
| format | Article |
| id | doaj-art-427f5c9e4fb740cda7d5bb960b9c1a6e |
| institution | DOAJ |
| issn | 1757-4676 1757-4684 |
| language | English |
| publishDate | 2016-05-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj-art-427f5c9e4fb740cda7d5bb960b9c1a6e2025-08-20T03:06:00ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842016-05-018893794810.15252/emmm.201506083The time‐of‐day of myocardial infarction onset affects healing through oscillations in cardiac neutrophil recruitmentMaximilian J Schloss0Michael Horckmans1Katrin Nitz2Johan Duchene3Maik Drechsler4Kiril Bidzhekov5Christoph Scheiermann6Christian Weber7Oliver Soehnlein8Sabine Steffens9Institute for Cardiovascular Prevention (IPEK), Ludwig‐Maximilians‐University (LMU) MunichInstitute for Cardiovascular Prevention (IPEK), Ludwig‐Maximilians‐University (LMU) MunichInstitute for Cardiovascular Prevention (IPEK), Ludwig‐Maximilians‐University (LMU) MunichInstitute for Cardiovascular Prevention (IPEK), Ludwig‐Maximilians‐University (LMU) MunichInstitute for Cardiovascular Prevention (IPEK), Ludwig‐Maximilians‐University (LMU) MunichInstitute for Cardiovascular Prevention (IPEK), Ludwig‐Maximilians‐University (LMU) MunichWalter‐Brendel‐Center of Experimental Medicine, Ludwig‐Maximilians‐University (LMU) MunichInstitute for Cardiovascular Prevention (IPEK), Ludwig‐Maximilians‐University (LMU) MunichInstitute for Cardiovascular Prevention (IPEK), Ludwig‐Maximilians‐University (LMU) MunichInstitute for Cardiovascular Prevention (IPEK), Ludwig‐Maximilians‐University (LMU) MunichAbstract Myocardial infarction (MI) is the leading cause of death in Western countries. Epidemiological studies show acute MI to be more prevalent in the morning and to be associated with a poorer outcome in terms of mortality and recovery. The mechanisms behind this association are not fully understood. Here, we report that circadian oscillations of neutrophil recruitment to the heart determine infarct size, healing, and cardiac function after MI. Preferential cardiac neutrophil recruitment during the active phase (Zeitgeber time, ZT13) was paralleled by enhanced myeloid progenitor production, increased circulating numbers of CXCR2hi neutrophils as well as upregulated cardiac adhesion molecule and chemokine expression. MI at ZT13 resulted in significantly higher cardiac neutrophil infiltration compared to ZT5, which was inhibited by CXCR2 antagonism or neutrophil‐specific CXCR2 knockout. Limiting exaggerated neutrophilic inflammation at this time point significantly reduced the infarct size and improved cardiac function.https://doi.org/10.15252/emmm.201506083circadian rhythmfibrosismyocardial infarction healingneutrophilsprogenitors |
| spellingShingle | Maximilian J Schloss Michael Horckmans Katrin Nitz Johan Duchene Maik Drechsler Kiril Bidzhekov Christoph Scheiermann Christian Weber Oliver Soehnlein Sabine Steffens The time‐of‐day of myocardial infarction onset affects healing through oscillations in cardiac neutrophil recruitment EMBO Molecular Medicine circadian rhythm fibrosis myocardial infarction healing neutrophils progenitors |
| title | The time‐of‐day of myocardial infarction onset affects healing through oscillations in cardiac neutrophil recruitment |
| title_full | The time‐of‐day of myocardial infarction onset affects healing through oscillations in cardiac neutrophil recruitment |
| title_fullStr | The time‐of‐day of myocardial infarction onset affects healing through oscillations in cardiac neutrophil recruitment |
| title_full_unstemmed | The time‐of‐day of myocardial infarction onset affects healing through oscillations in cardiac neutrophil recruitment |
| title_short | The time‐of‐day of myocardial infarction onset affects healing through oscillations in cardiac neutrophil recruitment |
| title_sort | time of day of myocardial infarction onset affects healing through oscillations in cardiac neutrophil recruitment |
| topic | circadian rhythm fibrosis myocardial infarction healing neutrophils progenitors |
| url | https://doi.org/10.15252/emmm.201506083 |
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