MicroRNAs are short non-coding RNA fragments involved in post-transcriptional gene silencing. Aberrant expression of microRNAs is increasingly recognized as important contributing factor in the pathogenesis of pulmonary hypertension. We recently identified a highly conserved signaling pathway involving the action of the microRNA miR-20a as regulator of the expression of bone morphogenetic protein receptor type II (BMPR2), which has been found mutated or dysregulated in several forms of pulmonary hypertension

Employing the hypoxia-induced model of pulmonary hypertension, we could demonstrate in vivo that the specific inhibition of miR-20a restores functional levels of BMPR2 and, in turn, prevents pulmonary arterial vascular remodeling. Treatment with antagomiR-20a enhanced the expression levels of BMPR2 in lung tissues; moreover, antagomiR-20a significantly reduced both thickness of vessel walls and luminal occlusion of small pulmonary arteries and, probably as hemodynamic consequence, decreased right ventricular hypertrophy. We further showed that transfection of human pulmonary arterial smooth muscle cells with antagomiR-20a increased the expression of p21 resulting in reduced cell proliferation.

In conclusion, we demonstrated for the first time that miR-20a can be specifically targeted in an in vivo model for pulmonary hypertension emphasizing that treatment with antagomiR-20a prevents the development of vascular remodeling.