Checkpoint kinase 1 promotes the development of pulmonary arterial hypertension
Checkpoint kinase 1 promotes the development of pulmonary arterial hypertension
复制标题
检查点激酶1促进肺动脉高压的发展
DOI：
10.1161/atvbaha.119.312969
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Shimokawa H
中科院分区：
文献类型：
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作者：
Satoh K;Kikuchi N;Kurosawa R;Shimokawa H
肺动脉高压（PAH）以肺动脉远端的组织学改变、血管周围炎症和纤维化改变以及右心室衰竭为特征。1-5除了遗传背景外，许多环境因素以及心脏病和炎症引起的容量超负荷也参与了PAH的发生。6-8在这个过程中，肺动脉平滑肌细胞（PASMCs）将受到转录因子的表观遗传修饰。9，10最近，我们报道了SeP（硒蛋白P）是一种致病蛋白，可诱导活性氧的产生并促进PAH-PASMCs的增殖（图）。9-11此外，已经证明过量的活性氧（氧化应激）会诱导PAH-PASMCs的DNA损伤。12-14 PAH患者PASMCs（PAH-PASMCs）的特征与健康对照不同。PAH-PASMCs的异常特征是基于其与癌细胞相似的细胞功能改变。2，13因此，PAH-PASMCs的这些特征可能成为治愈PAH患者的靶点。
Pulmonary arterial hypertension (PAH) is character-ized by histological changes in the distal pulmonary arteries, perivascular inflammation and fibrotic change, and right ventricular failure. 1–5 In addition to genetic backgrounds, many environmental factors as well as volume overload because of heart disease and inflammation are involved in the development of PAH. 6–8 In this process, pulmonary artery smooth muscle cells (PASMCs) will suffer epigenetic modifications by transcriptional factors. 9, 10 Recently, we have reported that SeP (selenoprotein P) is a pathogenic protein that induces the production of reactive oxygen species and promotes the proliferation of PAH-PASMCs (Figure). 9–11 Moreover, it has been demonstrated that excessive reactive oxygen species (oxidative stress) will induce DNA damage in PAH-PASMCs. 12–14 The characteristics of PASMCs in patients with PAH (PAH-PASMCs) are different from those of healthy controls. 9, 15 The abnormal features of PAH-PASMCs are based on their altered cellular functions similar to cancer cells. 2, 13 Thus, these features of PAH-PASMCs can potentially be a target to cure patients with PAH.