title: 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 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.
authors.affiliation: Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians-University (LMU) Munich, Munich, Germany.
authors.forename: Maximilian J
authors.initials: MJ
authors.lastname: Schloss
authors.affiliation: Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians-University (LMU) Munich, Munich, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Horckmans
authors.affiliation: Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians-University (LMU) Munich, Munich, Germany Max Delbrueck Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Nitz
authors.affiliation: Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians-University (LMU) Munich, Munich, Germany.
authors.forename: Johan
authors.initials: J
authors.lastname: Duchene
authors.affiliation: Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians-University (LMU) Munich, Munich, Germany German Centre for Cardiovascular Research (DZHK), partner site Munich Heart Alliance, Munich, Germany Department of Pathology, Amsterdam Medical Center (AMC), Amsterdam, The Netherlands.
authors.forename: Maik
authors.initials: M
authors.lastname: Drechsler
authors.affiliation: Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians-University (LMU) Munich, Munich, Germany.
authors.forename: Kiril
authors.initials: K
authors.lastname: Bidzhekov
authors.affiliation: Walter-Brendel-Center of Experimental Medicine, Ludwig-Maximilians-University (LMU) Munich, Munich, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Scheiermann
authors.affiliation: Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians-University (LMU) Munich, Munich, Germany German Centre for Cardiovascular Research (DZHK), partner site Munich Heart Alliance, Munich, Germany Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands.
authors.forename: Christian
authors.initials: C
authors.lastname: Weber
authors.affiliation: Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians-University (LMU) Munich, Munich, Germany German Centre for Cardiovascular Research (DZHK), partner site Munich Heart Alliance, Munich, Germany Department of Pathology, Amsterdam Medical Center (AMC), Amsterdam, The Netherlands.
authors.forename: Oliver
authors.initials: O
authors.lastname: Soehnlein
authors.affiliation: Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians-University (LMU) Munich, Munich, Germany German Centre for Cardiovascular Research (DZHK), partner site Munich Heart Alliance, Munich, Germany sabine.steffens@med.uni-muenchen.de.
authors.forename: Sabine
authors.identifier: 0000-0002-6892-9751
authors.initials: S
authors.lastname: Steffens
mesh_terms: D000818:Animals; D018925:Chemokines / Q000378:metabolism; D002940:Circadian Rhythm; D004195:Disease Models, Animal; D005260:Female; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000473:pathology* / Q000503:physiopathology; D020556:Neutrophil Infiltration
chemical_list: D018925:Chemokines
keywords: circadian rhythm; fibrosis; myocardial infarction healing; neutrophils; progenitors