Division of Hematology/Oncology, Department of Medicine, Warren Alpert Medical School of Brown University, Providence, Rhode Island.
Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, Rhode Island.
J Cell Physiol. 2019 Nov;234(11):21193-21198. doi: 10.1002/jcp.28723. Epub 2019 Apr 22.
Pulmonary hypertension (PH) is an incurable disease characterized by pulmonary vascular remodeling and ultimately death. Two rodent models of PH include treatment with monocrotaline or exposure to a vascular endothelial growth factor receptor inhibitor and hypoxia. Studies in these models indicated that damaged lung cells evolve extracellular vesicles which induce production of progenitors that travel back to the lung and induce PH. A study in patients with pulmonary myelofibrosis and PH indicated that 100 cGy lung irradiation could remit both diseases. Previous studies indicated that murine progenitors were radiosensitive at very low doses, suggesting that 100 cGy treatment of mice with induced PH might be an effective PH therapy. Our hypothesis is that the elimination of the PH-inducing marrow cells by low dose irradiation would remove the cellular influences creating PH. Here we show that low dose whole-body irradiation can both prevent and reverse established PH in both rodent models of PH.
肺动脉高压（PH）是一种不可治愈的疾病，其特征是肺血管重构，最终导致死亡。两种 PH 的啮齿动物模型包括使用单环素来治疗或暴露于血管内皮生长因子受体抑制剂和缺氧。这些模型中的研究表明，受损的肺细胞会产生细胞外囊泡，这些囊泡诱导祖细胞的产生，祖细胞会回到肺部并引发 PH。一项针对患有肺纤维化和 PH 的患者的研究表明，100cGy 的肺部照射可以同时缓解这两种疾病。先前的研究表明，在非常低的剂量下，鼠类祖细胞对辐射敏感，这表明用诱导 PH 的小鼠进行 100cGy 的治疗可能是一种有效的 PH 治疗方法。我们的假设是，低剂量照射消除诱导 PH 的骨髓细胞会消除导致 PH 的细胞影响。在这里，我们展示了全身低剂量照射既能预防又能逆转两种 PH 啮齿动物模型中的 PH。
