Table 5.

Progression of dysregulated pathways in volume overload over time

KEGG Pathways	Pulmonary Insufficiency at 1 mo	Pulmonary Insufficiency at 3 mo
Metabolism (glycolysis, TCA cycle, amino acid, ATP transporters)	↓	↓
Cell cycle	↓	↓
Calcium signaling	↓	↓
GPCR signaling	↓	↓
Wnt signaling	↓	↓↑
MAPK signaling	↓	↓↑
Degradation	↓	↓↑
Cell adhesion	↓	↓↑
TGF-β signaling	↓	↑
p53 signaling	↓	↑
Cytoskeleton	↓	↑
Repair of damaged DNA	—	↓
Regulation of transcription	—	↓
Ion channel activity	—	↓
NK cell-mediated cytotoxicity	—	↓
Insulin, mTOR signaling	—	↑
Adiopocytokine signaling	—	↑

Many of the pathways downregulated at 1 mo were also downregulated at 3 mo. No pathways were significantly upregulated at 1 mo. TGF-β and p53 signaling and c pathways related to the cytoskeleton were downregulated at 1 mo but demonstrated upregulation by 3 mo. Pathways related to Wnt, MAPK, degradation, and cell adhesion were downregulated at 1 mo. Over time, these pathways demonstrated areas of up- and downregulation. Several novel pathways became significant at 3 mo including insulin and adipocytokine signaling.