Hypoxia-induced mediators of stem/progenitor cell trafficking are increased in children with hemangioma
Hypoxia-induced mediators of stem/progenitor cell trafficking are increased in children with hemangioma
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DOI：
10.1161/atvbaha.107.150284
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发表时间：
2007-12-01
影响因子：
8.7
通讯作者：
Gurtner, Geoffrey C.
中科院分区：
文献类型：
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作者：
Kleinman, Mark E.;Greives, Matthew R.;Gurtner, Geoffrey C.
目的：目前尚不清楚婴儿血管瘤增生期新生血管形成的机制。众所周知，循环骨髓源性内皮祖细胞（EPCs）在缺血组织中使用由转录因子HIF- 1 α调节的介质形成新血管。内皮祖细胞的动员可通过VEGF-A、基质金属蛋白酶(MMP)-9和雌激素增强，而归巢则继发于基质细胞源性因子-1 α (SDF-1 α)的局部表达。我们研究了在婴儿血管瘤的增殖过程中，这些介导EPC贩运的介质是否被上调。方法与结果：从增殖性血管瘤患儿和年龄匹配的对照组（n=10，每组）获取手术标本和血液样本。测定血液中VEGF-A和MMP-9的水平，并分析组织切片中SDF-1 α、MMP-9、VEGF-A和HIF-1 α的含量。雌激素作为血管瘤内皮细胞生长调节剂的作用也进行了研究。我们发现所有这些介导EPC贩运的介质在患有增殖性婴儿血管瘤的儿童的血液和标本中都升高。在体外实验中，缺氧和雌激素联合使用对血管瘤内皮细胞增殖具有协同作用。结论：这些发现表明，增殖性血管瘤表达已知的血管生成介质，并提示该过程可能在该疾病的发生或进展中起作用。
Objective-The mechanism of neovascularization during the proliferative phase of infantile hemangioma is poorly understood. It is known that circulating bone marrow-derived endothelial progenitor cells (EPCs) form new blood vessels in ischemic tissues using mediators regulated by the transcription factor, HIF- 1 alpha. Mobilization of EPCs is enhanced by VEGF-A, matrix metalloproteinase (MMP)-9, and estrogen, whereas homing is secondary to localized expression of stromal cell-derived factor-1 alpha (SDF-1 alpha). We examined whether these mediators of EPC trafficking are upregulated during the proliferation of infantile hemangioma.Methods and Results-Surgical specimens and blood samples were obtained from children with proliferating hemangioma and age-matched controls (n=10, each group). VEGF-A and MMP-9 levels were measured in blood, and tissue sections were analyzed for SDF-1 alpha, MMP-9, VEGF-A, and HIF-1 alpha. The role of estrogen as a modulator of hemangioma endothelial cell growth was also investigated. We found that all these mediators of EPC trafficking are elevated in blood and specimens from children with proliferating infantile hemangioma. In vitro, the combination of hypoxia and estrogen demonstrated a synergistic effect on hemangioma endothelial cell proliferation.Conclusions-These findings demonstrate that proliferating hemangiomas express known mediators of vasculogenesis and suggest that this process may play a role in the initiation or progression of this disease.