title: Sham surgery and inter-individual heterogeneity are major determinants of monocyte subset kinetics in a mouse model of myocardial infarction.
abstract: OBJECTIVE
  Mouse models of myocardial infarction (MI) are commonly used to explore the pathophysiological role of the monocytic response in myocardial injury and to develop translational strategies. However, no study thus far has examined the potential impact of inter-individual variability and sham surgical procedures on monocyte subset kinetics after experimental MI in mice. Our goal was to investigate determinants of systemic myeloid cell subset shifts in C57BL/6 mice following MI by developing a protocol for sequential extensive flow cytometry (FCM).
  
  
  RESULTS
  Following cross-sectional multiplex FCM analysis we provide for the first time a detailed description of absolute quantities, relative subset composition, and biological variability of circulating classical, intermediate, and non-classical monocyte subsets in C57BL/6 mice. By using intra-individual longitudinal measurements after MI induction, a time course of classical and non-classical monocytosis was recorded. This approach disclosed a significant reduction of monocyte subset dispersion across all investigated time points following MI. We found that in the current invasive model of chronic MI the global pattern of systemic monocyte kinetics is mainly determined by a nonspecific inflammatory response to sham surgery and not by the extent of myocardial injury.
  
  
  CONCLUSIONS
  Application of sequential multiplexed FCM may help to reduce the impact of biological variability in C57BL/6 mice. Furthermore, the confounding influence of sham surgical procedures should always be considered when measuring monocyte subset kinetics in a murine model of MI.
authors.affiliation: Department of Cardiology, Kerckhoff Heart and Thorax Center, Bad Nauheim, Germany.
authors.forename: Jedrzej
authors.initials: J
authors.lastname: Hoffmann
authors.affiliation: Department of Cardiology, Kerckhoff Heart and Thorax Center, Bad Nauheim, Germany.
authors.forename: Manuel
authors.initials: M
authors.lastname: Ospelt
authors.affiliation: Department of Cardiology, Kerckhoff Heart and Thorax Center, Bad Nauheim, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Troidl
authors.affiliation: Department of Cardiology, Kerckhoff Heart and Thorax Center, Bad Nauheim, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Voss
authors.affiliation: Department of Cardiology, Kerckhoff Heart and Thorax Center, Bad Nauheim, Germany; Department of Cardiology, University of Giessen, Medical Clinic I, Giessen, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Liebetrau
authors.affiliation: Department of Cardiology, Kerckhoff Heart and Thorax Center, Bad Nauheim, Germany.
authors.forename: Won-Keun
authors.initials: WK
authors.lastname: Kim
authors.affiliation: Department of Cardiology, Kerckhoff Heart and Thorax Center, Bad Nauheim, Germany; Department of Cardiology, University of Giessen, Medical Clinic I, Giessen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Rolf
authors.affiliation: Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.
authors.forename: Astrid
authors.initials: A
authors.lastname: Wietelmann
authors.affiliation: Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Braun
authors.affiliation: Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Troidl
authors.affiliation: Department of Cell and Molecular Physiology, Health Sciences Division, Loyola University Chicago, Maywood, Illinois, United States of America.
authors.forename: Sakthivel
authors.initials: S
authors.lastname: Sadayappan
authors.affiliation: Department of Cell and Molecular Physiology, Health Sciences Division, Loyola University Chicago, Maywood, Illinois, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: Barefield
authors.affiliation: Department of Cardiology, Kerckhoff Heart and Thorax Center, Bad Nauheim, Germany; Department of Cardiology, University of Giessen, Medical Clinic I, Giessen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Hamm
authors.affiliation: Department of Cardiology, Kerckhoff Heart and Thorax Center, Bad Nauheim, Germany; Department of Cardiology, University of Giessen, Medical Clinic I, Giessen, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Nef
authors.affiliation: Department of Cardiology, Kerckhoff Heart and Thorax Center, Bad Nauheim, Germany; Department of Cardiology, University of Giessen, Medical Clinic I, Giessen, Germany.
authors.forename: Helge
authors.initials: H
authors.lastname: Möllmann
mesh_terms: D000818:Animals; D003430:Cross-Sectional Studies; D005434:Flow Cytometry; D007150:Immunohistochemistry; D007700:Kinetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000378:metabolism*; D009203:Myocardial Infarction / Q000601:surgery*