Different Expression of Hypoxic and Angiogenic Factors in Human Endometriotic Lesions

Different Expression of Hypoxic and Angiogenic Factors in Human Endometriotic Lesions
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DOI:
10.1177/1933719115607978
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发表时间:
2016-04-01
影响因子:
2.9
通讯作者:
Petraglia, Felice
Petraglia, Felice
中科院分区:
医学4区
文献类型:
--
作者:
Filippi, Irene;Carrarelli, Patrizia;Petraglia, Felice

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子宫内膜异位症与局部血管生成和缺氧机制有关。事实上,患有子宫内膜异位症的女性的腹腔液会产生特定的微环境来支持异位子宫内膜组织的生长和发育。本研究调查了不同子宫内膜异位症表型中促血管生成标记物与缺氧过程之间的关联,分析了患有不同形式子宫内膜异位症的非孕妇中与缺氧信号通路相关并参与血管生成过程的多个基因的表达。收集卵巢子宫内膜异位症(OMA;n = 16)或深部浸润性子宫内膜异位症(DIE;n = 11)的样本,此外,通过宫腔镜检查从健康女性身上收集对照子宫内膜。通过定量逆转录聚合酶链反应评估缺氧诱导因子(HIF)1/2α、蛋白酶激活受体(PAR)1/4和血管内皮生长因子(VEGF)A的基因表达。卵巢子宫内膜异位瘤表达高水平的 HIF-1/2 α、PAR-1/4 和 VEGF-A,而 DIE 与未受影响女性的子宫内膜相比,没有显示出显着不同的基因表达。 OMA中HIF-1/2α的表达与VEGF-A mRNA的表达呈正相关。总体数据指出,疾病的异质性反映了与缺氧和血管生成相关的基因表达水平的差异,表明此类条件可能在疾病的发展中发挥积极作用。
Endometriosis is associated with local angiogenic and hypoxic mechanisms. Indeed, peritoneal fluid of women with endometriosis generates a specific microenvironment to support the growth and development of ectopic endometrial tissues. The association between proangiogenic markers and hypoxic processes in different endometriosis phenotypes was investigated in the present study, analyzing the expression of several genes, related to hypoxic signaling pathway and involved in angiogenic processes, in nonpregnant women with different forms of endometriosis. Samples of ovarian endometrioma (OMA; n = 16) or deep infiltrating endometriosis (DIE; n = 11) were collected, and in addition, control endometrium was collected from healthy women by hysteroscopy. The gene expression of the hypoxia-inducible factors (HIF) 1/2 alpha, protease-activated receptors (PARs) 1/4, and vascular endothelial growth factor (VEGF) A was evaluated by quantitative reverse-transcription polymerase chain reaction. Ovarian endometrioma expresses high levels of HIF-1/2 alpha, PAR-1/4, and VEGF-A, while DIE did not show significantly different gene expression compared to endometrium from unaffected women. A positive correlation between the expression of HIF-1/2 alpha and VEGF-A mRNA was observed in OMA. The overall data point out that the heterogeneity of the disease reflects differences in expression levels of genes associated with hypoxia and angiogenesis, suggesting that such conditions may have an active role in the development of the disease.