Table 1. miRNAs involved in the pathogenesis of PAH.
| Cell type | miRNA | Target mRNA | Function of miRNA | Animal model | Reference |
|---|---|---|---|---|---|
| PASMC | miR-130 | CDKN1A | Increase of proliferation, no effects on apoptosis | Chronic hypoxia in mice | 104 |
| PAEC/PASMC | miR-17/20a | BMPR2/PDLIM5, CDKN1A | Increase of proliferation, SMC phenotypic switch | Chronic hypoxia in mice and MCT in rats | 64, 65, 105, 106 |
| PAEC/PASMC | miR-130/301 | PPARγ | Vasoconstriction, increase of proliferation | Chronic hypoxia+SU-5416 in mice, MCT in rats and chronic hypoxia in mice | 107, 108 |
| PASMC | miR-210 | MKP-1, E2F3 | Increase of proliferation, inhibition of apoptosis | Chronic hypoxia in mice | 109, 110 |
| PASMC | miR-451 | Increase of migration under serum-free conditions, no effect on proliferation | Chronic hypoxia in mice | 111 | |
| PASMC | miR-193-3p | IGF1R, ALOX5, ALOX12, ALOX15 | Inhibition of proliferation | MCT in rats and chronic hypoxia in mice | 112 |
| PASMC | miR-9 | Increase of proliferation, SMC phenotypic switch | 113 | ||
| PASMC | miR-190 | KCNQ5 | Vasoconstriction | Chronic hypoxia in rats | 114 |
| PAEC | miR-27a | PPARγ | Increase of proliferation | Chronic hypoxia in mice | 115 |
| Fibroblast | miR-124 | PTBP1, MCP-1 | Inhibition of proliferation, migration and inflammatory phenotype | Chronic hypoxia in mice and rats, chronic hypoxia+SU-5416 in mice | 36 |
| PASMC | miR-124 | CAMTA1, PTBP1, NFATc1 | Inhibition of proliferation, SMC phenotypic switch | Chronic hypoxia in mice | 116 |
| PASMC | miR-138 | MST1 | Inhibition of apoptosis | 117 | |
| PAEC | miR-424/503 | FGF2, FGFR1 | Inhibition of proliferation and migration, cell cycle arrest | MCT in rats and chronic hypoxia+SU-5416 in rats | 43 |
| PASMC | miR-206 | NOTCH-3 | Increase of proliferation and migration, inhibition of apoptosis, SMC phenotypic switch | Chronic hypoxia in mice | 118 |
| PASMC | miR-145 | ACE, DAB2, FSCN1 | Vascular remodeling | Chronic hypoxia in mice and miR-145 knockout mice | 119 |
| PASMC | miRNA-328 | IGF1R, CaV1.2 | Inhibition of proliferation, increase of apoptosis, vasoconstriction | Chronic hypoxia in rats and miR-328 transgenic mice | 120 |
| PASMC | miR-204 | SHP2 | Inhibition of proliferation, increase of apoptosis | MCT in rats | 121 |
Abbreviations: ACE, angiotensin-converting enzyme; ALOX5, arachidonate 5-lipoxygenase; ALOX12, arachidonate 12-lipoxygenase; ALOX15, arachidonate 15-lipoxygenase; BMPR2, bone morphogenetic protein receptor type II; CAMTA1, calmodulin-binding transcription activator 1; CaV1.2, L-type calcium channel 1C; CDKN1A, cyclin-dependent kinase inhibitor 1A; DAB2, disabled-2; E2F3, transcription factor E2F3; FGF2, fibroblast growth factor 2; FGFR1, fibroblast growth factor 1 receptor; FSCN1, fascin actin-bundling protein 1; IGF1R, insulin growth factor 1 receptor; KCNQ5, potassium voltage-gated channel subfamily KQT member 5 protein; MCP-1, monocyte chemotactic protein-1; MCT, monocrotaline; MKP-1, mitogen-activated protein kinase phosphatase-1; miRNA, microRNA; MST1, serine/threonine kinase 4; MYOCD, myocardin; NFATc1, nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1; NOTCH-3, neurogenic locus notch homolog 3 protein 3; PAEC, pulmonary artery endothelial cell; PAH, pulmonary arterial hypertension; PASMC, pulmonary artery smooth muscle cell; PDLIM5, PDZ and LIM domain protein 5; PPARγ, peroxisome proliferator–activated receptor-γ PTBP1, polypyrimidine tract-binding protein 1; SHP2, Src homology-2 domain containing protein tyrosine phosphatase 2.