PIM1 (Provirus Integration Site For Moloney Murine Leukemia Virus) as a Novel Biomarker and Therapeutic Target in Pulmonary Arterial Hypertension
PIM1 (Provirus Integration Site For Moloney Murine Leukemia Virus) as a Novel Biomarker and Therapeutic Target in Pulmonary Arterial Hypertension
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PIM1（莫洛尼鼠白血病病毒原病毒整合位点）作为肺动脉高压的新型生物标志物和治疗靶点
DOI：
10.1161/atvbaha.120.313975
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发表时间：
2020
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;Shimokawa H.
肺动脉高压（PAH）的特征是远端肺动脉的组织学变化、血管周围炎症以及由此导致的右心室衰竭。 1-5 除了几种特定的遗传背景外，某些环境因素以及心脏病和炎症性疾病导致的容量超负荷也与 PAH 的发生有关。 6-8 PAH肺血管病理变化的重要特征之一是肺动脉平滑肌细胞（PASMC）像癌细胞一样过度增殖和抵抗凋亡。 9 事实上，这些细胞表现出许多癌细胞共有的特征，为利用癌症治疗策略来治疗 PAH（癌症理论）提供了机会。 10 尽管 PAH 患者 PASMC (PAH-PASMC) 这种表型变化的主要触发因素仍不清楚，但过度氧化应激和炎症已被证明在 PAH 血管重塑的发展中发挥关键作用。已知这些围绕肺血管系统的环境变化会导致 DNA 损伤，这可能有利于 PAH 中观察到的增殖和抗凋亡表型的出现。越来越多的证据一致表明，PAH-PASMC 的 DNA 损伤反应 (DDR) 对于这种增殖表型改变的可持续性具有重要意义。 11
Pulmonary arterial hypertension (PAH) is characterized by histological changes in the distal pulmonary arteries, perivascular inflammation, and resultant right ventricular failure. 1–5 In addition to several specific genetic backgrounds, certain environmental factors, as well as volume overload due to heart disease and inflammatory disease, are involved in the development of PAH. 6–8 One of the important characteristics of pathological changes in pulmonary vasculature of PAH is an excessive proliferation and a resistance to apoptosis of pulmonary artery smooth muscle cells (PASMCs) like cancer cells. 9 Indeed, these cells exhibit many features common to cancer cells offering the opportunity to exploit therapeutic strategies used in cancer to treat PAH (cancer theory). 10 Although the primary trigger of such phenotypic changes of PASMCs from patients with PAH (PAH-PASMCs) still remains unclear, excessive oxidative stress and inflammation have been shown to play a key role in the development of vascular remodeling in PAH. These environmental changes surrounding pulmonary vasculature are known to cause DNA damage that might favor the emergence of the proproliferative and antiapoptotic phenotypes observed in PAH. Consistently, there is mounting evidence showing the importance of DNA-damage response (DDR) of PAH-PASMCs for the sustainability of such proproliferative phenotypic alterations. 11