This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hewett, P. Articles by Ahmed, A. Search for Related Content PubMed PubMed Citation Articles by Hewett, P. Articles by Ahmed, A.

(American Journal of Pathology. 2002;160:773-780.)
© 2002 American Society for Investigative Pathology

Short Communication

Down-Regulation of Angiopoietin-1 Expression in Menorrhagia

From the Department of Reproductive and Vascular Biology, TheMedical School, University of Birmingham, Edgbaston, Birmingham,United Kingdom

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.

This article has been cited by other articles:

				J.L. Brun, C. Galant, D. Delvaux, P. Lemoine, P. Henriet, P.J. Courtoy, and E. Marbaix Menstrual activity of matrix metalloproteinases is decreased in endometrium regenerating after thermal ablation Hum. Reprod., February 1, 2009; 24(2): 333 - 340. [Abstract] [Full Text] [PDF]

				Y.-L. Lee, Y. Liu, P.-Y. Ng, K.-F. Lee, C.-L. Au, E. H.-Y. Ng, P.-C. Ho, and W. S.-B. Yeung Aberrant expression of angiopoietins-1 and -2 and vascular endothelial growth factor-A in peri-implantation endometrium after gonadotrophin stimulation Hum. Reprod., April 1, 2008; 23(4): 894 - 903. [Abstract] [Full Text] [PDF]

				J. E. Girling, F. L. Lederman, L. M. Walter, and P. A. W. Rogers Progesterone, But Not Estrogen, Stimulates Vessel Maturation in the Mouse Endometrium Endocrinology, November 1, 2007; 148(11): 5433 - 5441. [Abstract] [Full Text] [PDF]

				W. S.N. Shim, I. A.W. Ho, and P. E.H. Wong Angiopoietin: A TIE(d) Balance in Tumor Angiogenesis Mol. Cancer Res., July 1, 2007; 5(7): 655 - 665. [Abstract] [Full Text] [PDF]

				O. P. Milling Smith, S. Battersby, K. J. Sales, H. O. D. Critchley, and H. N. Jabbour Prostacyclin Receptor Up-Regulates the Expression of Angiogenic Genes in Human Endometrium via Cross Talk with Epidermal Growth Factor Receptor and the Extracellular Signaling Receptor Kinase 1/2 Pathway Endocrinology, April 1, 2006; 147(4): 1697 - 1705. [Abstract] [Full Text] [PDF]

				H. N. Jabbour, R. W. Kelly, H. M. Fraser, and H. O. D. Critchley Endocrine Regulation of Menstruation Endocr. Rev., February 1, 2006; 27(1): 17 - 46. [Abstract] [Full Text] [PDF]

				N. R. Nayak, C. J. Kuo, T. A. Desai, S. J. Wiegand, B. L. Lasley, L. C. Giudice, and R. M. Brenner Expression, localization and hormonal control of angiopoietin-1 in the rhesus macaque endometrium: potential role in spiral artery growth Mol. Hum. Reprod., November 1, 2005; 11(11): 791 - 799. [Abstract] [Full Text] [PDF]

				S. Battersby, H. O. D. Critchley, K. Morgan, R. P. Millar, and H. N. Jabbour Expression and Regulation of the Prokineticins (Endocrine Gland-Derived Vascular Endothelial Growth Factor and Bv8) and Their Receptors in the Human Endometrium across the Menstrual Cycle J. Clin. Endocrinol. Metab., May 1, 2004; 89(5): 2463 - 2469. [Abstract] [Full Text] [PDF]

				J. Hirchenhain, I. Huse, A. Hess, P. Bielfeld, F. De Bruyne, and J. S. Krussel Differential expression of angiopoietins 1 and 2 and their receptor Tie-2 in human endometrium Mol. Hum. Reprod., November 1, 2003; 9(11): 663 - 669. [Abstract] [Full Text] [PDF]

				M. Hickey, G. Pillai, J.M. Higham, M. Sullivan, D. Horncastle, D. Doherty, and G. Stamp Changes in endometrial blood vessels in the endometrium of women with hormone replacement therapy-related irregular bleeding Hum. Reprod., May 1, 2003; 18(5): 1100 - 1106. [Abstract] [Full Text] [PDF]