Table 2.
MicroRNAs identified as involved in PAH
| miRNA | Function | References |
|---|---|---|
| miRNA-124 | Decreased levels in proliferating PA fibroblasts; overexpression contributes to mitotic arrest |
40 |
| miRNA-424/503 | Involved in the apelin pathway regulating FGF2 and PAEC proliferation | 41 |
| miRNA-204 | Suppresses BRD4 expression, which regulates multiple oncogenes; normally downregulated in hypoxia |
42, 43 |
| miRNA-126 | Decreased expression in decompensated right ventricular failure; expression upregulated in plexiform lesions |
44, 45 |
| miRNA-145/143 | Involved in PASMC migration and apoptosis, higher expression in concentric hypertrophy vs. plexiform lesions | 45 |
| miRNA-17/92 | Increased proliferation and decreased apoptosis, involved in the BMPR2 mutation pathway | 46, 47 |
| miRNA-21 | Increased proliferation and decreased apoptosis, appears to be part of hypoxia-mediated vascular response | 48, 49 |
| miRNA-27a | Involved in PPARγ pathway, increased expression propagates cellular proliferation | 50 |
| miRNA-138 | Induces apoptosis resistance, endothelial dysfunction via blocking eNOS activation | 51, 52 |
| miRNA-150 | Downregulated in PAH, prognostic value | 53 |
| miRNA-190 | Regulates hypoxic vasoconstriction via potassium channels | 54 |
| miRNA-206 | Decreased in hypoxia, part of HIF-1α pathway; decreased levels results in PASMC proliferation and decreased apoptosis | 55, 56 |
| miRNA-210 | Hypoxia inducible, inhibits PASMC apoptosis | 57 |
| miRNA-328 | Inhibited by hypoxia, suppression causes increased proliferation and vasoconstriction | 58 |
| miRNA-103/107 | Inhibition in hypoxia leads to increased levels of HIF-1α, HIF-1β, and PASMC proliferation | 59 |
| miRNA-9 | Increased in hypoxia, induces PASMC proliferation | 60 |
Note
BMPR2: bone morphogenetic protein receptor type 2; BRD4: bromodomain 4; eNOS: endothelial nitric oxide synthetase; FGF2: fibroblast growth factor 2; HIF-1: hypoxia-inducible factor 1; miRNA: microRNA; PA: pulmonary arterial; PAEC: pulmonary arterial endothelial cell; PAH: pulmonary arterial hypertension; PASMC: pulmonary arterial smooth muscle cell; PPARγ: peroxisome proliferator-activated receptor gamma.