miRNA-140-5p: new avenue for pulmonary arterial hypertension drug development?
miRNA-140-5p: new avenue for pulmonary arterial hypertension drug development?
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DOI：
10.2217/epi-2016-0089
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发表时间：
2016-09
期刊：
影响因子：
3.8
通讯作者：
A. Rothman;D. Rowlands;A. Lawrie
中科院分区：
文献类型：
--
作者：
A. Rothman;D. Rowlands;A. Lawrie
肺动脉高压（PAH）是一种罕见但致命的疾病。在病理学上，PAH的特征是通过中膜增厚、内膜纤维化和血管增生性病变的形成过程，持续的血管收缩和小肺动脉的进行性闭塞。目前的治疗靶向通过前列环素、内皮素或一氧化氮途径的持续血管收缩，但对解决潜在的进行性增殖性血管疾病几乎没有作用。已经在PAH中发现了microRNA（miR）表达失调，我们最近强调了PAH患者中miR-140- 5 p的减少。在动物模型中用Smurf 1调节替代miR-140- 5 p减轻疾病，Smurf 1是一种靶向BMPR 2的E3泛素连接酶，作为一种确定的机制。这些数据突出了Smurf 1抑制作为PAH的治疗。
Pulmonary arterial hypertension (PAH) is a rare but fatal disease. Pathologically, PAH is characterised by sustained vasoconstriction and progressive obliteration of small pulmonary arteries through a process of medial thickening, intimal fibrosis and the formation of angioproliferative lesions. Current treatments target the sustained vasoconstriction via either the prostacyclin, endothelin or nitric oxide pathway but do little to address the underlying progressive proliferative vascular disease. Dysregulated expression of microRNA (miR) has been identified in PAH and we have recently highlighted reduced miR-140-5p in patients with PAH. Replacement of miR-140-5p attenuated disease in animal models with the regulation of Smurf1, a E3 ubiquitin ligase targeting BMPR2 as one identified mechanism. These data highlight Smurf1 inhibition as a treatment for PAH.