Micro RNA ‐483 amelioration of experimental pulmonary hypertension

Endothelial dysfunction is critically involved in the pathogenesis of pulmonary arterial hypertension ( PAH ) and that exogenously administered micro RNA may be of therapeutic benefit. Lower levels of miR‐483 were found in serum from patients with idiopathic pulmonary arterial hypertension ( IPAH ), particularly those with more severe disease. RNA ‐seq and bioinformatics analyses showed that miR‐483 targets several PAH ‐related genes, including transforming growth factor‐β ( TGF ‐β), TGF ‐β receptor 2 ( TGFBR 2), β‐catenin, connective tissue growth factor ( CTGF ), interleukin‐1β ( IL ‐1β), and endothelin‐1 ( ET ‐1). Overexpression of miR‐483 in EC s inhibited inflammatory and fibrogenic responses, revealed by the decreased expression of TGF ‐β, TGFBR 2, β‐catenin, CTGF , IL ‐1β, and ET ‐1. In contrast, inhibition of miR‐483 increased these genes in EC s. Rats with EC ‐specific miR‐483 overexpression exhibited ameliorated pulmonary hypertension ( PH ) and reduced right ventricular hypertrophy on challenge with monocrotaline ( MCT ) or Sugen + hypoxia. A reversal effect was observed in rats that received MCT with inhaled lentivirus overexpressing miR‐483. These results indicate that PAH is associated with a reduced level of miR‐483 and that miR‐483 might reduce experimental PH by inhibition of multiple adverse responses.