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.

Abstract

BackgroundIntrauterine growth retardation (IUGR) is related to pulmonary artery hypertension in adults, and microRNA‐206 (miR‐206) is proposed to affect the proliferation and apoptosis of pulmonary artery smooth muscle cells (PASMCs) via post‐transcriptional regulation.Methods and ResultsIn an IUGR rat model, we found that the expression and function of potassium voltage‐gated channel subfamily A member 5 (Kv1.5) in PASMCs was inhibited, and pulmonary artery hypertension was exaggerated after chronic hypoxia (CH) treatment as adults. microRNA expression was investigated in PASMCs 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 PASMCs 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 IK v 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 KCNA5. Also, decreased right ventricular systolic pressure and cell proliferation were observed in PASMCs from 12‐week‐old control and IUGR rats after CH, while inhibitor did not significantly affect control and IUGR rats.ConclusionsThese 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 PASMCs exposed to hypoxia. Thus, miR‐206 may be a trigger for induction of exaggerated CH–pulmonary artery hypertension of IUGR via Kv1.5.