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

• DOI: 10.15252/emmm.201506083
• Publication Date: 2016-05-26T01:23:19Z
• Authors: Maximilian J Schloss; Michael Horckmans; Katrin Nitz; Johan Duchene; Maik Drechsler; Kiril Bidzhekov; Christoph Scheier...; Christian Weber; Oliver Soehnlein; Sabine Steffens
• Keywords: Chemokines -- metabolism; circadian rhythm; Medicine (General); info:eu-repo/classification/ddc/616.07; Myocardial Infarction; ddc:616.07; QH426-470; Inbred C57BL; Myocardial Infarction -- pathology -- physiopathology; Mice; 03 medical and health sciences; R5-920; neutrophils; Genetics; Animals; Research Articles; progenitors; 0303 health sciences; Myocardial Infarction/pathology/physiopathology; Animal; fibrosis; Sciences bio-médicales et agricoles; Chemokines/metabolism; Circadian Rhythm; 3. Good health; Mice, Inbred C57BL; Disease Models, Animal; myocardial infarction healing; Neutrophil Infiltration; Cardiovascular and Metabolic Diseases; Disease Models; Female; Chemokines

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.