Increased Expression of MicroRNA-206 Inhibits Potassium Voltage-Gated Channel Subfamily A Member 5 in Pulmonary Arterial Smooth Muscle Cells and Is Related to Exaggerated Pulmonary Artery Hypertension Following Intrauterine Growth Retardation in Rats.

Background Intrauterine growth retardation ( IUGR ) is related to pulmonary artery hypertension in adults, and mi croRNA -206 (miR-206) is proposed to affect the proliferation and apoptosis of pulmonary artery smooth muscle cells ( PASMC s) via post-transcriptional regulation. Methods and Results In an IUGR rat model, we found that the expression and function of potassium voltage-gated channel subfamily A member 5 (Kv1.5) in PASMC s was inhibited, and pulmonary artery hypertension was exaggerated after chronic hypoxia ( CH ) treatment as adults. micro RNA expression was investigated in PASMC s from 12-week-old male IUGR rats with CH by microarray, polymerase chain reaction, and in situ hybridization. The expression levels of Kv1.5 in primary cultured PASMC s and pulmonary artery smooth muscle from IUGR or control rats were evaluated with and without application of an miR-206 inhibitor. Right ventricular systolic pressure, cell proliferation, luciferase reporter assay, and I were also calculated. We found increased expression of miR-206 in resistance pulmonary arteries of IUGR rats at 12 weeks compared with newborns. Application of an miR-206 inhibitor in vivo or in vitro increased expression of Kv1.5 α-protein and KCNA 5. Also, decreased right ventricular systolic pressure and cell proliferation were observed in PASMC s from 12-week-old control and IUGR rats after CH , while inhibitor did not significantly affect control and IUGR rats. Conclusions These results suggest that expression of Kv1.5 and 4-aminopyridine (Kv channel special inhibitor)-sensitive Kv current were correlated with the inhibition of miR-206 in PA rings of IUGR - CH rats and cultured IUGR PASMC s exposed to hypoxia. Thus, miR-206 may be a trigger for induction of exaggerated CH-pulmonary artery hypertension of IUGR via Kv1.5.