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Abstract
AimsMouse 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).Methods and ResultsFollowing 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.ConclusionsApplication 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.
Highlights
Monocytes are key components of the innate host immune defense; the imbalance of monocytic responses with resulting prolonged inflammation may aggravate disease
Application of sequential multiplexed flow cytometry (FCM) may help to reduce the impact of biological variability in C57BL/6 mice
The occurrence of blood monocytosis was correlated with the extent of myocardial injury and with impaired myocardial salvage in patients following acute myocardial infarction (MI), and increased numbers of circulating monocytes were found to predict impaired infarct healing and plaque progression in atherosclerotic mice [6,7]
Summary
Monocytes are key components of the innate host immune defense; the imbalance of monocytic responses with resulting prolonged inflammation may aggravate disease. Different human monocyte subsets have been postulated to play distinct roles during infection as well as in sterile inflammatory disorders, including atherosclerosis, acute myocardial infarction (MI), congestive heart failure, multiple sclerosis, and cancer [1,2]. Mouse models of MI are commonly used to explore the basic pathophysiological and prognostic role of the monocytic response following myocardial injury. The occurrence of blood monocytosis was correlated with the extent of myocardial injury and with impaired myocardial salvage in patients following acute MI, and increased numbers of circulating monocytes were found to predict impaired infarct healing and plaque progression in atherosclerotic mice [6,7]. Abrogating blood monocytosis to counteract the progression of atherosclerotic disease or to improve infarct healing in mice may emerge as a promising future approach to the treatment of ischemic heart diseases in humans [8,9]. No study far has examined the impact of biological inter-individual variability and invasive sham procedures on monocyte subset kinetics and development of monocytosis after experimental MI in mice
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