Open AccessIncreased 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
Author(s) -
Lv Ying,
Fu Linchen,
Zhang Ziming,
Gu Weizhong,
Luo Xiaofei,
Zhong Ying,
Xu Shanshan,
Wang Yu,
Yan Lingling,
Li Min,
Du Lizhong
Publication year - 2019
Publication title -
journal of the american heart association
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.494
H-Index - 85
ISSN - 2047-9980
DOI - 10.1161/jaha.118.010456
Subject(s) - pulmonary artery , pulmonary hypertension , potassium channel , medicine , in situ hybridization , endocrinology , hypoxia (environmental) , biology , gene expression , cardiology , chemistry , gene , biochemistry , organic chemistry , oxygen
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 K 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 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.