Elevated monocyte-specific type I interferon signalling correlates positively with cardiac healing in myocardial infarct patients but interferon alpha application deteriorates myocardial healing in rats

Figures

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  Fig. 1. Increased IFN type I expression in monocytes of MI patients with a decreased EDVi baseline–4-month FU. a The change in LV EDVi from baseline to 4-month follow-up. b The change in LV EF from baseline to 4-month follow-up. c Heat map showing the expression of genes of the MOSERLE_IFNA_RESPONSE pathway supervised by the change in LV EDVi from baseline to 4-month follow-up. Each column represents one patient. Patients with a decreased LV EDVi at 4-month follow-up are placed on the left side (n = 14) and patients with an increased LV EDVi on the right side (n = 37). Red denotes relatively high gene expression, green represents relatively low-expressed genes. Note the relative high expression of genes of the MOSERLE_IFNA_RESPONSE pathway in patients with a decreased LV EDVi at 4-month post-MI (right side). Statistical analyses are performed using the Student’s t test. EDVi end-diastolic volume index, EF ejection fraction, FU follow-up, LV left ventricular

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  Fig. 2. IFN-α administration results in ventricular dilatation in rats. 2D echocardiography measurements at day 28 showing a images of the M-mode parameters LVIDd and LVIDs which are quantified and presented in b and c showing mean ± SD. d Relative change in LVIDd and LVIDs presented as FS(%). Short axis of the LV area at day 28 in diastole in e (image) and f (quantification) as well as in systole in g (image) and h (quantification). MI myocardial infarction, IFN-α interferon alpha, LVIDd left ventricle internal diameter in diastole and LVIDs left ventricle internal diameter in systole. Statistical analysis are performed using the Student’s t test

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  Fig. 3. IFN-α administration increases the necrotic tissue area at day 3 and the total infarct size at day 28. a Images of a rat myocardial PTAH stain at day 3 with the infarcted area indicated by a yellow line. Scale bar represents 2 mm. b Quantification of the infarcted areas at day 3. c Magnification of the PTAH stain showing the infarcted area with necrotic (n) and granulation tissue (g) indicated by yellow lines and the viable myocardium (v) indicated by white lines. Scale bar represents 200 µm. d Quantification of necrotic and granulation tissue in the infarcted area at day 3. P values were calculated using the Mann–Whitney U test. e Quantification of the infarcted area at day 28 and f its quantification of granulation and fibrotic tissue. PTAH phosphotungstic acid–hematoxylin, MI myocardial infarction, IFN-α interferon alpha. Statistical analyses are performed using the Student’s t test (b and e) or the Mann–Whitney U test (d and f)

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  Fig. 4. IFN-α changes the distribution of circulating monocyte subsets at day 2 following experimental MI. a Representative flow cytometry plots of mononuclear cells at baseline, days 2, 3 and 28. After baseline, rats were subdivided into groups (MI or MI + IFN-α). b Quantification of the pro-inflammatory CD43-lo monocytes in MI and in IFN-α-treated MI rats (red bars) at the different time points. MI myocardial infarction, IFN-α interferon alpha. Statistical analyses are performed using the Student’s t test (paired and unpaired)

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  Fig. 5. IFN-α does not alter total macrophage infiltration in the myocardium but increases alternative macrophage infiltration into the myocardium at day 3. Immunohistochemical images of the infarcted myocardium at day 3 (a–b) and day 28 (c–d) of CD68 (a and c) staining of all macrophages and CD163 (b and d) representing the reparative alternative macrophages. Scale bar represents 50 µm. Quantification of CD68 at day 3 (e) and day 28 (g) and the quantification of the macrophage subsets at day 3 (f) and day 28 (h). MI myocardial infarction, IFN-α interferon alpha. Data are presented as box plots showing the median and 25th–75th percentile together with the minimum and the maximum values. Statistical analyses are performed using the Mann–Whitney U test (unpaired) or the Wilcoxon signed rank test (paired)