Table 3.
A List of Well-Established Dysregulated miRNAs in PAH
| miRNA | Changes in PH | Sample type | Targets | Function | (Ref. #) |
|---|---|---|---|---|---|
| miR-29 | ↓ |
Hypoxic PH rat PAAFs | α-SMA, extracellular matrix collagen | Fibrosis | (44) |
| MCT PH rat PASMCs | Collagen I | (45) | |||
| (in adaptative RV hypertrophy) ↑ |
Fetally-implanted aortopulmonary shunt ovine | Collagen A1, Collagen 3A1 | (37) | ||
| miR-124 | ↓ | Human PAH PASMCs | NFAT | PASMC proliferation | (46) |
| Human PAH PAAFs and human PAH PAECs | PTPB1, MCP-1 | Proliferation | (47, 48, 49) | ||
| miR-140 | ↓ ↑ |
MCT PH rat PASMCs | TNF-α | PASMC proliferation | (50) |
| SU/Hx/Nx and MCT PH rat PASMCs | SMURF1 | PASMC proliferation | (51) | ||
| Human hypoxia PASMCs | SOD2 | PASMC proliferation | (52) | ||
| SU/Hx/Nx PH rat RV | MFN1 | Apoptosis of cardiac myocytes | (53) | ||
| miR-204 | ↓ | Human PAH PASMCs | HIF-1α | PASMC proliferation | (54) |
| Human PAH PASMCs | RUNX2 | PASMC proliferation | (55) | ||
| Human PAH and MCT PH rats PASMCs | SHP2, Src kinase, NFAT | PASMC proliferation | (56) | ||
| Human PAH and hypoxia rat PAECs | ATG7 | Autophagy | (57) | ||
| miR-210 | ↑ | Hypoxic PH rat PASMCs | ISCU | PASMC proliferation | (58) |
| E2F3 | PASMC proliferation | (59) | |||
| MKP-1 | PASMC proliferation | (60) | |||
| miR-1 | ↑ ↓ |
Plasma human PAH and Su/Hx/Nx PH rat lungs | SOD1, Cx43, CAV2, KLF4 | Endothelial dysfunction | (61) |
| SU/Hx/Nx PH rat lungs | KCNA5 | PASMC hypertrophy | (62) | ||
| Human PAH and hypoxic PH rat PASMCs | SphK1 | PASMC proliferation | (63) | ||
| MCT PH rat RV | TGFβ | RV hypertrophy | (64) | ||
| miR-130/301 | ↑ | SU/Hx/Nx mouse model | EDN1 | Vasoconstriction | (65) |
| MCT PH mouse PAECs | BMPR2 | Lung vascular remodeling | (66) | ||
| Pulmonary fibrosis mouse lung | PPARγ-APOE-LRP8 | Fibrosis | (67) | ||
| miR-138 | ↑ | Hypoxic PH rat PASMCs | Mst1 | PASMC proliferation | (68) |
| Human PAH PASMCs | MCUC | PASMC proliferation | (69) | ||
| Human PAH PASMCs | TASK-1 | PASMC proliferation | (70) | ||
| miR-17∼92 | ↑ | Human PAH PAECs | BMPR2 | PAEC survival | (71) |
| Hypoxic PH mouse and MCT PH rat lungs | p21 | PASMC proliferation | (72) | ||
| Human PAH PASMCs | PDLIM5 | PASMC dedifferentiation | (73) | ||
| Hypoxic PH mouse PASMCs | PHD2 | PASMC proliferation | (74) | ||
| miR-21 | ↑ | Human PAH PAECs | BMPR2, RhoB | Decrease angiogenesis and vasodilation | (75) |
| Human PAH PASMCs | PTEN | PASMC proliferation | (76,77) | ||
| Human PAH lung tissue | DDAH1 | PASMC proliferation | (78) | ||
| Hypoxia PH mouse lung | BMPR2 | PASMC proliferation | (79) | ||
| miR-214 | ↑ | Human PAH PASMCs | PTEN, CCNL2 | PASMC proliferation | (80,81) |
| Hypoxia PASMCs | ARHGEF12 | PASMC proliferation | (82) | ||
| Human PAH PASMCs | MEF2C, MYOCD, SMC | PASMC proliferation | (83) | ||
| miR-223 | ↓ | Human PAH PASMCs | PARP-1 | PASMC proliferation | (84) |
| Hypoxia PH mouse and rat lung and hypoxia PASMCs | RhoB, MYPT1, MLC2 | PASMC proliferation | (85) | ||
| MCT PH rat PASMCs | ITGB3 | PASMC proliferation | (86) | ||
| miR-424 | ↑ | Human plasma and MCT PH rat PAECs | SMURF1, BMPR2 | RV hypertrophy | (28) |
| ↓ | SU/Hx/Nx, MCT PH rat and human PAH PAECs | FGF2, FGFR1 | PASMC proliferation | (87) |
MCT = monocrotaline; PAAF = pulmonary arterial adventitial fibroblasts; PAEC = pulmonary artery endothelial cell; PASMC = pulmonary artery smooth muscle cell; PH = pulmonary hypertension; RV = right ventricle; SU/Hx/Nx = association of Sugen 5416 with chronic hypoxia followed by normoxia; other abbreviation as in Table 1.