Die Bedeutung der Angiogenese für die Pathogenese der Endometriose

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Angiogenesis in ectopic endometrium is crucial for endometriosis pathogenesis and lesion activity, as shown by VEGF and MMP mRNA expression correlating with vascularity in a CAM assay.

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The paper discusses how implantation of ectopic endometrial tissue is a key step in endometriosis pathogenesis and argues that angiogenesis is both a prerequisite for implantation and a parameter reflecting lesion activity. Using a chorioallantoic membrane (CAM) assay model with ectopic endometrial fragments, the authors analyzed time-dependent mRNA expression of VEGF and matrix metalloproteinases MMP1 and MMP2 and correlated these molecular changes with angiogenesis assessed by a vessel density index. They report an increase in angiogenic factors and an increase in angiogenic reaction over time, implying a link between angiogenic signaling and implanting aggressiveness. The study’s main limitation is that these findings are derived from an experimental CAM model rather than directly from human lesions in vivo. This paper is centrally about endometriosis — it focuses on how angiogenesis (VEGF/MMP-related activity) supports implantation and lesion activity in the pathogenesis of endometriosis.

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Abstract

The pathogenesis of endometriosis is dependent on implantation. Therefore, angiogenesis of the ectopic endometrium is discussed as a crucial step in the development of an endometriotic lesion. It is not only the main condition for implantation, but also a parameter for the clinical activity of endometriosis. Pigmented and non-pigmented endometriotic lesions differ according to their clinical activity and angiogenic potential. Using a model system of endometriosis, the chorioallantoic membrane assay, mRNA expression of VEGF and matrix metalloproteinases 1 and 2 was analysed. As the most representative angiogenic factors, they were correlated to the angiogenic reaction on the CAM by the vessel index. We assume that angiogenic activity of ectopic endometrium is a condition sine qua non for the pathogenesis of endometriosis, but is regulated by different other factors.
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Subscribe to RSS DOI: 10.1055/s-2003-42278 © Georg Thieme Verlag Stuttgart · New York Die Bedeutung der Angiogenese für die Pathogenese der Endometriose The Importance of Angiogenesis for the Pathogenesis of EndometriosisPublication History Publication Date: 23 September 2003 (online) Zusammenfassung Für die Pathogenese der Endometriose ist der Vorgang der Implantation der Schlüsselpunkt, der darüber entscheidet, ob ektope Endometriumzellen zum Krankheitsbild der Endometriose führen oder nicht. Voraussetzung für die Implantation ist die Expression angiogenetisch relevanter Faktoren, die die Angiogenese induzieren. Dabei ist für die Implantationsaggressivität die angiogenetische Aktivität der Läsionen entscheidend. Die Angiogenese ist somit nicht nur Bedingung, sondern auch ein wichtiger Parameter für die Aktivität der Erkrankung. Bisherige Studien am Chorioallantoismembran (CAM) Modell, einem dynamischen Modell der Endometriose, untersuchten den Implantationsprozess ektoper Endometriumfragmente. Analysiert wurde im Zeitverlauf die mRNA Expression des vaskulären endothelialen Wachstumsfaktors (VEGF) sowie der Matrix-Metalloproteinasen (MMP)1 und -2. Anhand der zeitgleichen Bestimmung des Gefäßdichteindexes der CAM konnten diese Ergebnisse mit der Angiogenese korreliert werden. Es konnte ein Anstieg der angiogenetischen Faktoren sowie ein Anstieg der Angiogenese gemessen werden. Abstract The pathogenesis of endometriosis is dependent on implantation. Therefore, angiogenesis of the ectopic endometrium is discussed as a crucial step in the development of an endometriotic lesion. It is not only the main condition for implantation, but also a parameter for the clinical activity of endometriosis. Pigmented and non-pigmented endometriotic lesions differ according to their clinical activity and angiogenic potential. Using a model system of endometriosis, the chorioallantoic membrane assay, mRNA expression of VEGF and matrix metalloproteinases 1 and 2 was analysed. As the most representative angiogenic factors, they were correlated to the angiogenic reaction on the CAM by the vesselindex. We assume that angiogenic activity of ectopic endometrium is a conditio sine qua non for the pathogenesis of endometriosis, but is regulated by different other factors. Schlüsselwörter Endometriose - Angiogenese - VEGF - Matrix-Metalloproteinase (MMP) - Aktivität - Implantation Key words Endometriosis - angiogenesis - VEGF - MMP - activity - implantation Literatur - 1 Brooks P C, Montgomery A M, Rosenfeld M, Reisfeld R A, Hu T, Klier G, Cheresh D A. Integrin alpha v beta 3 antagonists promote tumor regression by inducing apoptosis of angiogenic blood vessels. Cell. 1994; 79 1157-1164 - 2 Bruner K L, Matrisian L M, Rodgers W H, Gorstein F, Osteen K G. 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Expression of interstitial collagenase (matrix metalloproteinase-1) is related to the activity of human endometriotic lesions. Fertil Steril. 1997; 68 246-251 - 14 Kressin P, Wolber E M, Meyhöfer-Malik A, Diedrich K, Malik E. A modified chorioallontoic membrane (CAM) assay for testing antiangiogenic strategies in a model of experimentally induced endometriosis. Hum Reprod. 1999; 14 18 - 15 Kressin P, Wolber E M, Wodrich H, Meyhöfer-Malik A, Buchweitz O, Diedrich K, Malik E. Vascular endothelial growth factor mRNA in eutopic and ectopic endometrium. Fertil Steril. 2001; 76 1220-1224 - 16 Kressin P, Diedrich K, Malik E. Endometriose und Angiogenese. Der Gynäkologe. 2002; 35 224-231 - 17 Mahmood T A, Templeton A. Prevalence and genesis of endometriosis. Hum Reprod. 1991; 6 544-549 - 18 Malik E, Kressin P, Drenkhan M, Meyhöfer-Malik A, Wolber E M, Diedrich K. Koexpression von Angiopoietin-1, Angiopoietin-2 und VEGF165 im Endometrium auf der Chorioallontoismembran. XVII. Akademische Tagung Deutsch sprechender Hochschullehrer, Salzburg 2001 - 19 Malik E, Kressin P, Buchweitz O, Diedrich K. Endometriose und Aktivität. Der Gynäkologe. 2002; 35 232-237 - 20 McLaren J, Prentice A, Charnock- Jones D S, Smith S K. Vascular endothelial growth factor (VEGF) concentrations are elevated in peritoneal by fluid of women with endometriosis. Hum Reprod. 1996 b; 11 220-223 - 21 McLaren J, Prentice A, Charnock-Jones D S, Millican S A, Muller K H, Sharkey A M, Smith S K. Vascular endothelial growth factor is produced peritoneal fluid makrophages in endometriosis and is regulated by ovarian steroids. J Clin Invest. 1996 a; 98 (2) 482-489 - 22 Nisolle M, Casanas-Roux F, Anaf V, Mine J M, Donnez J. Morphometric study of the stromal vascularization in peritoneal endometriosis. Fertil Steril. 1993; 59 681-684 - 23 Osteen K G, Bruner-Tran K L, Ong D, Eisenberg E. Paracrine mediators of endometrial matrix metalloproteinase expression. Potential targets for progestin-based treatment of endometriosis. Ann NY Acad Sci. 2002; 955 139-146 - 24 Potuondo J A, Herran C, Echanojauregui A D, Riego A G. Peritoneal flushing and biopsy in laparoscopically diagnosed endometriosis. Fertil Steril. 1982; 38 538-541 - 25 Runnebaum B, Rabe T. Die Endometriose der Frau aus immunologischer und biologischer Sicht. Frauenarzt. 1995; 1 93-97 - 26 Salamonsen L A, Woolley D E. Matrix metalloproteinases in normal menstruation. Hum Reprod. 1996; 11 (Suppl 2) 124-133 - 27 Sampson J A. Peritoneal endometriosis due to the menstruational dissemination of endometrial tissue into the peritoneal cavity. Am J Obstet Gynecol. 1927; 14 422-469 - 28 Smith S K. Regulation of angiogenesis in the endometrium. Trends Endocrinol Metab. 2001; 12 147-151 - 29 Vernon M W, Beard J S, Graves K, Wilson E A. Classification of endometriotic implants by morphologic appearance and capacitiy to synthesize prostaglandin F. Fertil Seril. 1986; 46 801-806 - 30 Wenzl R J, Heinzl H. Localization of matrix metalloproteinase-2 in uterine endometrium and ectopic implants. Gynecologic and Obstetric Investigation. 1998; 45 253-257 - 31 Wolber E M, Kressin P, Meyhofer-Malik A, Diedrich K, Malik E. Differential induction of matrix metalloproteinase 1 and 2 in ectopic endometrium. Reprod Biomed Online. 2003; 6 238-243 - 32 Yancopoulos G D, Davis S, Gale N W, Rudge J S, Wiegand S J, Holash J. Vascular specific growth factors and blood vessel formation. Nature. 2000; 407 242-248 Dr. med. D. M. Gescher Universitätsklinikum der RWTH Aachen · Frauenklinik für Gynäkologie und Geburtshilfe Pauwelstraße 30 520741 Aachen Phone: 02 41/8 08 84 01

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Condition tags

endometriosisdie_deep_infiltrating

MeSH descriptors

Endometriosis Neovascularization, Pathologic Disease Progression Endometriosis Endometriosis Endometriosis Female Humans Matrix Metalloproteinase 1 Matrix Metalloproteinase 1 Matrix Metalloproteinase 2 Matrix Metalloproteinase 2 Neovascularization, Pathologic Neovascularization, Pathologic RNA, Messenger RNA, Messenger Vascular Endothelial Growth Factor A Vascular Endothelial Growth Factor A

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