Propranolol treatment of infantile hemangioma endothelial cells: A molecular analysis.
Propranolol treatment of infantile hemangioma endothelial cells: A molecular analysis.
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DOI：
10.3892/etm.2012.654
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发表时间：
2012-10
影响因子：
2.7
通讯作者：
Bryan BA
中科院分区：
文献类型：
--
作者：
Stiles J;Amaya C;Pham R;Rowntree RK;Lacaze M;Mulne A;Bischoff J;Kokta V;Boucheron LE;Mitchell DC;Bryan BA
婴儿血管瘤 (IH) 是一种非恶性、主要是皮肤血管肿瘤，约 5-10% 的儿童不同程度地受到影响。在生命的第一年，这些肿瘤会强烈增殖，平均大小达到 2 至 20 厘米。这些病变随后稳定下来，自发缓慢消退，并在 5 至 10 岁时完全消退。使用非选择性 β-肾上腺素能受体阻滞剂普萘洛尔对婴儿进行全身治疗已证明在减少 IH 的大小和外观方面具有显着疗效。然而，这种情况发生的机制在很大程度上尚不清楚。在这项研究中，我们试图了解β受体阻滞剂治疗 IH 的有效性的分子机制。我们的数据显示，普萘洛尔治疗 IH 内皮细胞以及一组正常的原代内皮细胞，可阻断内皮细胞增殖、迁移和肌动蛋白细胞骨架的形成，这与血管内皮生长因子受体 2 (VEGFR-2)、p38 和丝切蛋白信号传导的改变一致。此外，普萘洛尔会诱导关键细胞周期蛋白和细胞周期蛋白依赖性激酶抑制剂的蛋白质水平发生重大变化，并调节整体基因表达模式，对参与脂质/甾醇代谢、细胞周期调节、血管生成和泛素化的基因产生特别影响。有趣的是，普萘洛尔的作用与内皮细胞类型无关，其对 IH 内皮细胞特性的影响水平与在新生儿真皮微血管和冠状动脉内皮细胞中观察到的水平相似。该数据表明，虽然普萘洛尔显着抑制血管瘤和正常内皮细胞功能，但其缺乏内皮细胞特异性，暗示该药物治疗 IH 的功效可能比之前认为的简单阻断内皮功能更为复杂。
Infantile hemangiomas (IHs) are non-malignant, largely cutaneous vascular tumors affecting approximately 5–10% of children to varying degrees. During the first year of life, these tumors are strongly proliferative, reaching an average size ranging from 2 to 20 cm. These lesions subsequently stabilize, undergo a spontaneous slow involution and are fully regressed by 5 to 10 years of age. Systemic treatment of infants with the non-selective β-adrenergic receptor blocker, propranolol, has demonstrated remarkable efficacy in reducing the size and appearance of IHs. However, the mechanism by which this occurs is largely unknown. In this study, we sought to understand the molecular mechanisms underlying the effectiveness of β blocker treatment in IHs. Our data reveal that propranolol treatment of IH endothelial cells, as well as a panel of normal primary endothelial cells, blocks endothelial cell proliferation, migration, and formation of the actin cytoskeleton coincident with alterations in vascular endothelial growth factor receptor-2 (VEGFR-2), p38 and cofilin signaling. Moreover, propranolol induces major alterations in the protein levels of key cyclins and cyclin-dependent kinase inhibitors, and modulates global gene expression patterns with a particular affect on genes involved in lipid/sterol metabolism, cell cycle regulation, angiogenesis and ubiquitination. Interestingly, the effects of propranolol were endothelial cell-type independent, affecting the properties of IH endothelial cells at similar levels to that observed in neonatal dermal microvascular and coronary artery endothelial cells. This data suggests that while propranolol markedly inhibits hemangioma and normal endothelial cell function, its lack of endothelial cell specificity hints that the efficacy of this drug in the treatment of IHs may be more complex than simply blockage of endothelial function as previously believed.
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影响因子：
1.4
作者：
Mohammadi, Ali Akbar;Bakhshaeekia, Alireza;Mohammadi, Mohammad Kazem
通讯作者：
Mohammadi, Mohammad Kazem
影响因子：
3.7
作者：
Lichtenstein, N;Geiger, B;Kam, Z
通讯作者：
Kam, Z
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
2.7
作者：
Lashbrook, BL;Steinle, JJ
通讯作者：
Steinle, JJ
影响因子：
3.2
作者：
Boye E;Olsen BR
通讯作者：
Olsen BR