Table 1.

Targets and effects of relevant microRNAs

miRNA	Target and Effect
miR-17/92	Antagomir attenuates PH in animal models by directly targeting BMPR2.
miR-20a	Antagomir prevents development of remodeling in PH animal models by directly targeting BMPR2 (21).
miR-302	Cyclic feedback relationship with BMPR2, inhibits PASMC proliferation and migration.
miR-21	Reduces expression of BMPR2, though in vivo inhibitors attenuate hypoxic vasoconstriction and subsequent vascular remodeling; targets the HIF pathway.
miR-322	Acts upon BMPR1a and SMADs and promotes proliferation of PASMCs.
miR-125a	Increases protein concentrations of BMPR2 in PAECs leading to inhibition of cell proliferation. Hypoxia leads to upregulation of miR-125a in mouse models. However, in human subjects with PH, miR-125a circulating levels are decreased when compared with normal controls (78).
miR-138 and miR-25	Impair calcium signaling via downregulation of a component of the mitochondrial calcium uniporter. This increases cytosolic calcium within pulmonary arterial SMCs leading to vasoconstriction and a proproliferative environment (76).
miR-204 and BRD4	Downregulation of miR-204 leads to upregulation of the “epigenetic reader” bromodomain-containing protein 4 (BRD4), which, in turn, leads to overexpression of the oncogenes NFAT, survivin, and Bcl-2. The upregulation of these genes has been implicated in abnormal cellular proliferation in cancer cells, as well as in patients with pulmonary hypertension (106).

PH, pulmonary hypertension; BMPR2, bone-morphogenetic protein receptor-2; PASMCs, pulmonary artery smooth muscle cells; HIF, hypoxia-inducible factor; PAECs, pulmonary artery endothelial cells; SMCs, smooth muscle cells.