Figure 2. Mpc1^CKO mice upregulate several deleterious pathways upon I/R.

(A) Principal component analysis plot showing gene expression profiles of WT (normal: n = 13, ischemic: n = 7, nonischemic: n = 7) and Mpc1^CKO (normal: n = 6, ischemic: n = 4, nonischemic: n = 4) data sets. (B) Bar graph showing the distribution of significant genes within experimental conditions. (C) Volcano plot of genes identified using IPA in the Mpc1^CKO ischemic myocardium, including Slc16a3 (MCT4, black box). (D) Heatmap of genes associated with glycolysis in WT and Mpc1^CKO hearts and their response to I/R injury showing an upregulation of Slc16a3 in MPC1^CKO hearts. (E) IPA pathway analysis reveals that within the ischemic tissue of Mpc1^CKO hearts there is an association with deleterious pathways such as interleukin signaling, macrophage activation, cytokine storm activity, and cell death. (F) qRT-PCR showing Slc16a3 expression is normally low in both WT and Mpc1^CKO hearts but upon I/R injury Slc16a3 gene expression is upregulated in the ischemic and nonischemic samples of only the Mpc1^CKO. (G and H) The relative protein abundance via Western blotting of MCT4 and MPC1 in the nonischemic and ischemic myocardium reveal an unbalanced pyruvate-lactate metabolic axis following I/R injury. 2-way ANOVAs with a Tukey’s HSD post hoc test were used for statistical analysis between WT (n = 5) and Mpc1^CKO (n = 4), and ischemic, nonischemic, and normal (WT: n = 4, Mpc1^CKO: n = 4) tissue (F–H). *P < 0.05, **P < 0.01, ***P < 0.001. Values are represented as mean±SEM.