Fig. 5: MerTK+ macrophage transfer restores cardiac repair in ATF3-CKO mice.

a, Scheme showing sorted MerTK−and MerTK+ macrophages transferred into ATF3-CKO mice via intramyocardial injection. b,c, Flow cytometry analysis (b) and immunostaining (c) of Calcein AM+MerTK− and Calcein AM+MerTK+ macrophages in hearts of ATF3-CKO mice transferred with MerTK− or MerTK+ macrophages (n = 6 mice per group). Scale bars, 20 μm. d–g, Immunostaining (d) and flow cytometry analysis (e) of CD31+ ECs, EF (f) and fibrosis (g) in the hearts of the two groups (n = 6 mice per group). h, GO enrichment analysis based on upregulated DEGs in sorted Trem2+, MHCII+ and Lyve1+ macrophages compared with MerTK− macrophages. i, Tube formation assay in ECs cocultured with sorted MerTK+ and MerTK− macrophages (n = 10 biologically independent samples per group). Scale bar, 100 μm. j, Predicted interactions between MerTK+ cardiac macrophage-derived ligands and receptors expressed on ECs using CellChat receptor–ligand interaction analysis. k, Relative mRNA expression of Igf1 in sorted MerTK+ and MerTK− macrophages from hearts after IR (n = 6 mice per group). l, IGF1 levels in the culture supernatants of sorted MerTK+ and MerTK− macrophages from the hearts via ELISA (n = 8 biologically independent samples per group). m, Tube formation assay in ECs transfected with siRNA-NC or siRNA-IGF1R and then cocultured with sorted MerTK+ macrophages (n = 10 biologically independent samples per group). Scale bars, 100 μm. n, Relative mRNA levels of Igf1 in hearts from WT mice, ATF3-CKO mice and ATF3-CKO mice injected with MerTK+ macrophages (n = 6 mice per group). Statistical significance was evaluated using two-tailed, unpaired Student’s t-tests (d–g,i,m), unpaired Mann–Whitney U-tests (k,l), one-way ANOVA followed by Tukey’s multiple-comparison test (n), two-way ANOVA followed by Tukey’s multiple-comparison test (b) and Fisher’s exact test (h,j). All data are presented as mean ± s.e.m.