Hypoxia, hormones, and endothelial progenitor cells in hemangioma
Hypoxia, hormones, and endothelial progenitor cells in hemangioma
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DOI：
10.1089/lrb.2007.1014
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发表时间：
2007-01-01
影响因子：
1.4
通讯作者：
Gurtner, Geoffrey C.
中科院分区：
文献类型：
--
作者：
Chang, Edward I.;Chang, Eric I.;Gurtner, Geoffrey C.
血管瘤是婴儿期最常见的肿瘤，尽管这些病变的自然史已得到很好的描述，但其病因仍不清楚。目前的一种理论将血管瘤的形成归因于胎盘来源的细胞。然而，缺乏确凿的证据支持胎盘起源。虽然胎盘组织和血管瘤确实具有分子相似性，但这些相似之处可能是内皮细胞和血管祖细胞对相似环境线索的类似反应的结果。具体来说，这两种组织类型均由存在于低氧、高雌激素环境中的活跃增殖细胞组成。缺氧环境导致缺氧诱导因子-1α（HIF-1α）反应性趋化因子的上调，例如基质细胞衍生因子-1α（SDF-1α）和血管内皮生长因子（VEGF），已知这两种因子都能促进内皮祖细胞的募集和增殖。产后激素水平升高进一步加剧了这些病变的生长。在该模型中，HIF-1a 稳定性的增强与雌激素水平的增加相结合，创造了促进新血管发育的环境，最终导致婴儿血管瘤的发病机制。
Hemangiomas are the most common tumor of infancy, and although the natural history of these lesions is well described, their etiology remains unknown. One current theory attributes the development of hemangiomas to placentally-derived cells; however, conclusive evidence to support a placental origin is lacking. While placental tissue and hemangiomas do share molecular similarities, it is possible that these parallels are the result of analogous responses of endothelial cells and vascular progenitors to similar environmental cues. Specifically, both tissue types consist of actively proliferating cells that exist within a low oxygen, high estrogen environment. The hypoxic environment leads to an upregulation of hypoxia inducible factor-la (HIF-1 alpha) responsive chemokines such as stromal cell derived factor-la (SDF-1 alpha) and vascular endothelial growth factor (VEGF), both of which are known to promote the recruitment and proliferation of endothelial progenitor cells. Increased hormone levels in the postpartum period further potentiate the growth of these lesions. In this model, increased stabilization of HIF-1a in concert with increased levels of estrogen create a milieu that promotes new blood vessel development, ultimately contributing to the pathogenesis of infantile hemangiomas.