Figure 4.

Changes in the cardiac proteome during pregnancy and postpartum period. Proteomics analyses from hearts extracted from nonpregnant, diestrus (NP), midpregnant (MP; day 8 of pregnancy), late pregnant (LP; day 16 of pregnancy), and 1 wk postbirth (PB) female mice (n = 5 per group). A: unsupervised analysis was performed and a heatmap generated showing the top 75 differentially expressed proteins in hearts from NP, MP, LP, and PB female mice. Red indicates increased abundance, and blue indicates reduced abundance. Intensity of color indicates increased significance. B: supervised analysis showing partial least squares discriminant analysis (PLS-DA) highlighting group separation. C: the variable importance in projection plot (VIP) of the top 25 proteins contributing to the group separation observed in the PLS-DA plot. ANOVA analysis was performed to identify significantly expressed cardiac metabolite and protein abundances [P < 0.05; false discovery rate (FDR) 0.05] across all time points (NP, MP, LP, and PB). Human Metabolome Database (HMDB) and Uniprot IDs of those significantly expressed targets were added to the joint pathway analysis tool in Metaboanalyst 5.0., which corresponded to 493 changed metabolites and 350 changed proteins across all 4 time points. D and E: joint pathway analysis was performed with Fisher’s exact test with degree centrality topology applied and these data integrated based on pathway level combined P values for all pathways (D) and metabolic pathways (E).