title: Down-regulation of angiopoietin-1 expression in menorrhagia.
abstract: 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.
authors.affiliation: Department of Reproductive and Vascular Biology, TheMedical School, University of Birmingham, Edgbaston, Birmingham, United Kingdom.
authors.forename: Peter
authors.initials: P
authors.lastname: Hewett
authors.forename: Sarbjit
authors.initials: S
authors.lastname: Nijjar
authors.forename: Munjiba
authors.initials: M
authors.lastname: Shams
authors.forename: Susan
authors.initials: S
authors.lastname: Morgan
authors.forename: Janesh
authors.initials: J
authors.lastname: Gupta
authors.forename: Asif
authors.initials: A
authors.lastname: Ahmed
mesh_terms: D000328:Adult; D042683:Angiopoietin-1; D042702:Angiopoietin-2; D015536:Down-Regulation; D004717:Endometrium / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D008595:Menorrhagia / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics; D042787:Receptor, TIE-2
chemical_list: D042683:Angiopoietin-1; D042702:Angiopoietin-2; D008562:Membrane Glycoproteins; D011506:Proteins; D012333:RNA, Messenger; D020794:Receptor Protein-Tyrosine Kinases; D042787:Receptor, TIE-2