Down-regulation of angiopoietin-1 expression in menorrhagia

被引:48
作者
Hewett, P [1 ]
Nijjar, S [1 ]
Shams, M [1 ]
Morgan, S [1 ]
Gupta, J [1 ]
Ahmed, A [1 ]
机构
[1] Univ Birmingham, Sch Med, Dept Reprod & Vasc Biol, Birmingham B15 2TT, W Midlands, England
基金
英国医学研究理事会; 英国惠康基金;
关键词
D O I
10.1016/S0002-9440(10)64899-7
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
Angiogenesis Is an essential component of endometrial repair and regeneration following menses. Perturbation of this process is associated with menorrhagia, a common gynecological disorder that results in excessive menstrual bleeding. Angiopoietin-1 (Ang-1) promotes vascular maturation via the Tie-2 receptor, while angiopoietin-2 (Ang-2) is its natural antagonist that destabilizes vessels and initiates neovascularization in the presence of vascular endothelial growth factor. To test the hypothesis that menorrhagia arises as a result of poor signal for vascular maturation, we have examined the expression of Ang-1, Ang-2 and Tie-2 in endometrium throughout the menstrual cycle from 30 normal women and 28 patients with menorrhagia. Ribonuclease protection assay and Western blot analysis showed Ang-2 expression was consistently higher than Ang-1 in normal endometrium throughout the cycle. However, with menorrhagia Ang-1 mRNA and protein were not detected or down-regulated, while Ang-2 was observed at similar levels in both normal and menorrhagic endometrium resulting in a greater than a 50% decrease in the ratio of Ang-1 to Ang-2 protein. In situ hybridization and immunohistochemical studies supported these findings and revealed cyclical changes in the expression of Ang-1 and Ang-2. These results suggest that the angiopoietin/Tie-2 system promotes vascular remodeling in endometrium. and loss of normal Ang-1 expression may contribute to the excessive blood loss observed in menorrhagia.
引用
收藏
页码:773 / 780
页数:8
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