The time-of-day of myocardial infarction onset affects healing through oscillations in cardiac neutrophil recruitment

Maximilian J. Schloss, Michael Horckmans, Katrin Nitz, Johan Duchene, Maik Drechsler, Kiril Bidzhekov, Christoph Scheiermann, Christian Weber, Oliver Soehnlein, Sabine Steffens*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

84 Citations (Web of Science)

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 CXCR2(hi) 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.
Original languageEnglish
Pages (from-to)937-948
JournalEMBO Molecular Medicine
Volume8
Issue number8
DOIs
Publication statusPublished - Aug 2016

Keywords

  • circadian rhythm
  • fibrosis
  • myocardial infarction healing
  • neutrophils
  • progenitors

Cite this