Transient but Not Genetic Loss of miR-451 is Protective in the Development of Pulmonary Arterial Hypertension:

Pulmonary Circulation

Jennifer S.Grant¹ 

关键词: microRNA;    pulmonary vascular disorder;    hypoxia;    smooth muscle cell;    migration;   

DOI  :  10.1086/674751

学科分类：医学（综合）

来源: Sage Journals

【 摘 要 】

MicroRNAs are small noncoding RNAs involved in the regulation of gene expression and have recently been implicated in the development of pulmonary arterial hypertension (PAH). Previous work has established that miR-451 is upregulated in rodent models of PAH. The role of miR-451 in the pulmonary circulation is unknown. We therefore sought to assess the involvement of miR-451 in the development of PAH. Silencing of miR-451 was performed in vivo using miR-451 knockout mice and an anti-miR targeting mature miR-451 in rats. Coupled with exposure to hypoxia, indices of PAH were assessed. The effect of modulating miR-451 on human pulmonary artery smooth muscle cell proliferation and migration was analyzed. We observed a reduction in systolic right ventricular pressure in hypoxic rats pretreated with anti-miR-451 compared with hypoxia alone (47.7 ± 1.36 mmHg and 56.0 ± 2.03 mmHg, respectively; P < .01). In miR-451 knockout mice, compared with wild-type hypoxic mice, no significant differences were observed following exposure to chronic hypoxia. In vitro analysis demonstrated that overexpression of miR-451 in human pulmonary artery smooth muscle cells promoted migration under serum-free conditions. No effect on cellular proliferation was observed. In conclusion, transient inhibition of miR-451 attenuated the development of PAH in hypoxia-exposed rats. Genetic deletion of miR-451 had no beneficial effect on indices of PAH, potentially because of pathway redundancy compensating for the loss of miR-451.

【 授权许可】

CC BY