RT Journal Article
T1 miR‐1 is increased in pulmonary hypertension and downregulates Kv1.5 channels in rat pulmonary arteries
A1 Mondejar Parreño, Gema
A1 Callejo Arranz, María
A1 Barreira, Bianca
A1 Morales Cano, Daniel
A1 Esquivel Ruiz, Sergio Antonio
A1 Moreno Gutiérrez, Laura
A1 Cogolludo Torralba, Ángel Luis
A1 Pérez Vizcaíno, Francisco
AB Key pointsThe expression of miR‐1 is increased in lungs from the Hyp/Su5416 PAH rat model.Pulmonary artery smooth muscle cells from this animal model are more depolarized and show decreased expression and activity of voltage‐dependent potassium channel (Kv)1.5.miR‐1 directly targets Kv1.5 channels, reduces Kv1.5 activity and induces membrane depolarization.Antagomir‐1 prevents Kv1.5 channel downregulation and the depolarization induced by hypoxia/Su5416 exposition.AbstractImpairment of the voltage‐dependent potassium channel (Kv) plays a central role in the development of cardiovascular diseases, including pulmonary arterial hypertension (PAH). MicroRNAs are non‐coding RNAs that regulate gene expression by binding to the 3′‐untranslated region region of specific mRNAs. The present study aimed to analyse the effects of miR‐1 on Kv channel function in pulmonary arteries (PA). Kv channel activity was studied in PA from healthy animals transfected with miR‐1 or scrambled‐miR. Kv currents were studied using the whole‐cell configuration of the patch clamp technique. The characterization of the Kv1.5 currents was performed with the selective inhibitor DPO‐1. miR‐1 expression was increased and Kv1.5 channels were decreased in lungs from a rat model of PAH induced by hypoxia and Su5416. miR‐1 transfection increased cell capacitance, reduced Kv1.5 currents and induced membrane depolarization in isolated pulmonary artery smooth muscle cells. A luciferase reporter assay indicated that KCNA5, which encodes Kv1.5 channels, is a direct target gene of miR‐1. Incubation of PA with Su5416 and hypoxia (3% O2) increased miR‐1 and induced a decline in Kv1.5 currents, which was prevented by antagomiR‐1. In conclusion, these data indicate that miR‐1 induces pulmonary artery smooth muscle cell hypertrophy and reduces the activity and expression of Kv channels, suggesting a pathophysiological role in PAH.
PB Wiley
SN 0022-3751
SN 1469-7793
YR 2018
FD 2018-05-02
LK https://hdl.handle.net/20.500.14352/116913
UL https://hdl.handle.net/20.500.14352/116913
LA eng
NO Mondejar-Parreño G, Callejo M, Barreira B, et al. miR-1 is increased in pulmonary hypertension and downregulates Kv1.5 channels in rat pulmonary arteries. J Physiol. 2018; 00: 00–00. https://doi.org/10.1113/JP276054
NO Ministerio de Economía y Competitividad (España)
NO Unión Europea
DS Docta Complutense
RD 18 abr 2025