Department of Obstetrics and Gynecology, Maimonides Medical Center, Brooklyn, NY 11219, USA.
Hum Reprod Update. 2014 Mar-Apr;20(2):194-216. doi: 10.1093/humupd/dmt042. Epub 2013 Sep 29.
It is well established that tumors are dependent on angiogenesis for their growth and survival. Although uterine fibroids are known to be benign tumors with reduced vascularization, recent work demonstrates that the vasculature of fibroids is grossly and microscopically abnormal. Accumulating evidence suggests that angiogenic growth factor dysregulation may be implicated in these vascular and other features of fibroid pathophysiology.
Literature searches were performed in PubMed and Google Scholar for articles with content related to angiogenic growth factors and myometrium/leiomyoma. The findings are hereby reviewed and discussed.
Multiple growth factors involved in angiogenesis are differentially expressed in leiomyoma compared with myometrium. These include epidermal growth factor (EGF), heparin-binding-EGF, vascular endothelial growth factor, basic fibroblast growth factor, platelet-derived growth factor, transforming growth factor-β and adrenomedullin. An important paradox is that although leiomyoma tissues are hypoxic, leiomyoma feature down-regulation of key molecular regulators of the hypoxia response. Furthermore, the hypoxic milieu of leiomyoma may contribute to fibroid development and growth. Notably, common treatments for fibroids such as GnRH agonists and uterine artery embolization (UAE) are shown to work at least partly via anti-angiogenic mechanisms.
Angiogenic growth factors play an important role in mechanisms of fibroid pathophysiology, including abnormal vasculature and fibroid growth and survival. Moreover, the fibroid's abnormal vasculature together with its aberrant hypoxic and angiogenic response may make it especially vulnerable to disruption of its vascular supply, a feature which could be exploited for treatment. Further experimental studies are required in order to gain a better understanding of the growth factors that are involved in normal and pathological myometrial angiogenesis, and to assess the potential of anti-angiogenic treatment strategies for uterine fibroids.
肿瘤的生长和存活依赖于血管生成，这一点已得到充分证实。虽然子宫肌瘤被认为是血管化程度降低的良性肿瘤，但最近的研究表明，子宫肌瘤的血管在宏观和微观上都是异常的。越来越多的证据表明，血管生成生长因子失调可能与肌瘤的血管和其他病理生理学特征有关。
在 PubMed 和 Google Scholar 中进行了文献检索，检索内容与血管生成生长因子和子宫肌/平滑肌瘤相关。现将这些发现进行综述和讨论。
与子宫肌层相比，多种参与血管生成的生长因子在平滑肌瘤中表达不同。这些因子包括表皮生长因子（EGF）、肝素结合表皮生长因子、血管内皮生长因子、碱性成纤维细胞生长因子、血小板衍生生长因子、转化生长因子-β和肾上腺髓质素。一个重要的悖论是，尽管平滑肌瘤组织缺氧，但平滑肌瘤的关键缺氧反应分子调节剂下调。此外，平滑肌瘤的缺氧环境可能有助于肌瘤的发展和生长。值得注意的是，子宫肌瘤的常见治疗方法，如 GnRH 激动剂和子宫动脉栓塞术（UAE），至少部分是通过抗血管生成机制发挥作用的。
血管生成生长因子在肌瘤病理生理学机制中起着重要作用，包括异常血管生成和肌瘤的生长和存活。此外，肌瘤异常的血管以及其异常的缺氧和血管生成反应可能使其特别容易受到血管供应中断的影响，这一特征可能被用于治疗。需要进一步的实验研究，以更好地了解参与正常和病理性子宫肌层血管生成的生长因子，并评估抗血管生成治疗策略治疗子宫肌瘤的潜力。
