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

Myocardial infarction (MI) is the leading cause of death in Western countries. Epidemiological studies show acute MI to be more preva- lent in the morning and to be associated with a poorer outcome in terms of mortality and recovery. The mechanisms behind this asso- ciation 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 produc- tion, increased circulating numbers of CXCR2hi neutrophils as well as upregulated cardiac adhesion molecule and chemokine expres- sion. MI at ZT13 resulted in significantly higher cardiac neutrophil infiltration compared to ZT5, which was inhibited by CXCR2 antago- nism or neutrophil-specific CXCR2 knockout. Limiting exaggerated neutrophilic inflammation at this time point significantly reduced the infarct size and improved cardiac function. Keywords