Table 4.
Pathways involving the genes associated with the differentially methylated promoters between aortic and mitral valve tissue and their implication in valve development and disease.
| Pathway | Description | Development | Disease |
|---|---|---|---|
| TGFB signaling | Transforming growth factor beta signaling | EMTa (50) | ECMb remodeling (51), MVPc (52), ASd (53, 54) |
| NOTCH signaling | EMT (50), (55) | BAVe (55, 56), AS (55) and fetal cardiac defects (57) | |
| FGF signaling | Fibroblast growth factor signaling | EMT (58) | Valve malformation (58) |
| WNT signaling | heart, EMT (39, 50) | ||
| Cadherin signaling | EMT (59) | ||
| PDGF signaling | Platelet-derived growth factor | heart (60) | |
| VEGF signaling | EMT (50) | ||
| Integrin signaling | EMT (50), cell-ECM (61, 62) | ||
| HIF-1 signaling | RMVf, MMVg (63) | ||
| Angiogenesis | RMV (64) | ||
| IL-17 signaling | IEh (65) | ||
| NF-κB signaling | AS (66) | ||
| TNF signaling | AS (67) | ||
| Osteoclast differentiation pathways | AS (68) | ||
| Endothelin signaling | VICsi regulation by VECsj (69) | AS (70) | |
| Apoptotic pathways | AS (71) | ||
| PPAR signaling | lipid metabolism (72) |
a
EMT, endothelial mesenchymal trans-differentiation;
b
ECM, extracellular matrix;
c
MVP, mitral valve prolapse;
d
AS, aortic valve stenosis;
e
BAV, bicuspid aortic valve;
f
RMV, rheumatic mitral valve;
g
MMV, myxomatous mitral valve;
h
IE, infective endocarditis;
i
VICs, valve interstitial cells;
j
VECs, valve endothelial cells.