Stabilin-1+/SMA- macrophages in diagnostics of postinfarction tissue inflammation associated with adverse cardiac remodeling in patients with myocardial infarction (original) (raw)

European Heart Journal, 2020

Abstract

Introduction Molecular biomarkers of monocytes/macrophages identified to date have provided advanced diagnostic capabilities. We have accumulated a large amount of knowledge related to the role of innate immune response in the development of postinfarction cardiac remodeling. However, there is no significant advancement in clinical studies. Purpose The purpose was to assess prospects of macrophage biomarkers in diagnostics of postinfarction tissue inflammation associated with adverse cardiac remodeling in patients with myocardial infarction (MI). Methods The study included 41 patients with MI type 1, died in 2013–2014. We used a biobank of tissue samples for analysis. Group 1 (n=24) comprised patients who died within 72 hours of MI (the inflammatory phase), group 2 (n=17) comprised patients who died 4–28 days after MI (the regenerative phase). Macrophage infiltration in the heart was assessed by double immunofluorescence. We used stabilin-1 as a marker of M2 macrophages, while α-smooth muscle actin (α-SMA) was considered as a marker of cell transdifferentiation. Cells were counted in the infarct (IA) and non-infarct area (NIA). Morphological determination of adverse cardiac remodeling was based on the ratio of heart size, in particular, length/width ratio that was <1.1. Results We identified subpopulations of stabilin-1+/α-SMA− and stabilin-1+/α-SMA+ macrophages. In the IA the number of stabilin-1+/α-SMA− macrophages was lower during the inflammatory phase than during the regenerative phase (Table 1). The calculation of sensitivity and specificity of stabilin-1+/α-SMA− macrophages in the NIA for predicting of adverse cardiac remodeling has shown following: AUC=0.96, p<0.001. The cut-off value was 18 cells/mm2. The ROC curve is presented in Figure 1. Conclusions We identified that number of stabilin-1+/α-SMA− macrophages in the NIA ranged from 0 to 18 cells/mm2 was associated with adverse cardiac remodeling. The presence of stabilin-1+/α-SMA+ macrophages could indicate persistent tissue inflammation and possibility of macrophage transdifferentiation and plasticity. Our study supports prospects for implementation of macrophage biomarkers in clinical practice that might become a breakthrough in the development of new methods for management of MI and following complications. Figure 1 Funding Acknowledgement Type of funding source: None

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