Figure 3. Trajectories of proteomic changes in guinea pig heart failure progression implicate retinoid pathways from early to late stages.

(A) Hierarchically clustered heatmap of differentially regulated proteins in guinea pig HF progression (LIMMA, P < 0.05). Groups include the control (Ctrl; n = 3), 2 weeks of ACi protocol (2wk; n = 3), and 4 weeks of the ACi protocol (4wk; n = 3); 924 of 4150 were deemed significantly regulated. Careful inspection of the heatmap revealed 8 observable clusters corresponding to trajectories of protein expression. (B) Identification of proteins whose group means (z score normalized) most closely correlated (Pearson’s r > 0.975) with the 8 observed trajectories of up or downregulation. Numbers in parentheses indicate the number of proteins classified in each group; 620 of 924 proteins met the strict correlation criterion. (C) Pathway analysis was performed on proteins whose trajectories were classified as early, progressive, or late movers (Fisher’s exact test). After Benjamini-Hochberg correction, retinoid pathways were identified (P < 0.05). An RXR pathway was implicated in early and progressive trajectories. Several proteins downregulated at 4 weeks only contributed to the identification of the RAR activation pathway.