Fig 1: ADAM10 inhibition after MI reduces neutrophil chemotaxis-associated gene expression and CX3CL1 serum levels.a Principal components analysis (PCA) of transcriptomes of sham-operated (Sham, n = 3), GI254023X (A10i, n = 4) and DMSO (n = 4) treated mice 3 days after myocardial infarction. Principal components were computed for each sample using gene expression. The first two principal components (PC1 and PC2) are shown. The percent of variance explained by each component is reported in parentheses. b Volcano plot representing the expression changes of all genes. Significantly down- and upregulated genes (FDR < 0.01) are colored navy and magenta, respectively. Genes that do not show significant expression changes are colored gray. Examples of neutrophil chemotaxis-associated genes are labeled with gene names. P-values were calculated using the R packages DESeq2 R (v1.30.1)52 and IHW (1.18.0)53. Functional annotation clustering for the gene ontology (GO) terms c biological process and d molecular function of genes with significantly decreased expression upon A10i treatment (Fisher exact test with Benjamini-Hochberg posttest). e, f Gene set enrichment analysis of genes with significantly decreased expression upon A10i treatment performed on GO terms. Gene set enrichment analysis was performed using the GSEA tool (v4.1.0) of the Broad Institute55 and the DESeq2 R package (v1.30.1)52. g In-depth analysis of the significantly downregulated genes of the indicated functional annotation clusters. h Quantification of CXCL1 (n = 4 vs. 5, P = 0.380952), CXCL5 (n = 8 vs. 8, P = 0.633877), CXCL16 (n = 10 vs. 8, P = 0.572604), CX3CL1 (n = 9 vs. 9, P = 0.00399), IL-1ß (n = 8 vs. 8, P = 0.000155) and IL-6 (n = 6 vs. 5, P = 0.452381), serum levels in A10i and DMSO treated mice 3 days after MI (mean ± SEM, ns not significant, **P < 0.01, ***P < 0.001, two-tailed Mann–Whitney test). i Western blot analysis and j, k quantification of j CX3CL1 and k IL-1ß in heart tissue lysates of sham-operated (Sham) and LAD-ligated (MI) mice 3 days after infarction (n = 5, mean ± SEM, ns not significant, *P < 0.05, **P < 0.01, Kruskal–Wallis test with Dunn’s posttest, exact P-values are provided in the Source Data file). l Western blot analysis and m quantification of CX3CL1 in heart tissue lysates from patients with ischemic cardiomyopathy (ICM) and non-failing controls (NF) (n = 6, mean ± SEM, **P = 0.0031, two-tailed t test). Source data are provided as a Source Data file.