Zyklische Expression von Vascular Endothelial Growth Factor (VEGF), Angiopoetin 1 und 2 im Endometrium

Zusammenfassung

Hintergrund: Für die zyklischen Veränderungen des Endometriums ist die Angiogenese wesentlich mitverantwortlich. Eine physiologische Angiogenese wird durch die kombinierten Aktivitäten einer Vielzahl von Wachstumsfaktoren gesteuert, zu deren klassischen Vertretern der Vascular Endothelial Growth Factor (VEGF) und die Angiopoetine 1 (Ang1) und 2 (Ang2) gehören. Material und Methoden: In der vorliegenden Arbeit wurde die zyklische Angiogeneseaktivität des gesunden Endometriums anhand der Proben von 22 Patientinnen immunhistochemisch untersucht. Dabei wurde die Proteinlokalisation von VEGF, Ang1 und Ang2 im Drüsen- und Stromakompartiment untersucht. Weiterhin erfolgte die semiquantitative Beurteilung und die Untersuchung der Expressionsmuster dieser drei Faktoren in der Proliferations- und Sekretionsphase. Ergebnisse: Sowohl in den Drüsen als auch im Stroma zeigte sich eine Proteinexpression von VEGF, Ang1 und Ang2. Bei allen drei Faktoren war diese in den Drüsen signifikant höher als im Stroma. Für VEGF und Ang1 fanden sich weder in den Drüsen noch im Stroma signifikante Unterschiede in der Expression in den verschiedenen Zyklusphasen. Im Drüsenkompartiment ergab sich für Ang2 ein vergleichbares Resultat. Im Stroma hingegen zeigte sich eine signifikant höhere Ang2-Expression während der Proliferationsphase im Vergleich zur Sekretionsphase. Schlussfolgerung: Die vorliegenden Ergebnisse legen nahe, dass Ang2 in der Proliferationsphase des Zyklus die angiogenetische Wirkung des VEGF unterstützt. In der Sekretionsphase dagegen ermöglicht die niedrigere Ang2-Expression eine stabilisierende Wirkung des Ang1 auf das Gefäßendothel.

Abstract

Background: Physiologically, angiogenesis is responsible for maintaining normal reproductive function, cyclic endometrial growth and remodeling. Angiogenesis is induced by the expression of angiogenetic factors such as vascular endothelial growth factor (VEGF), angiopoetin 1 (Ang1) and angiopoetin 2 (Ang 2). Material and Methods: Endometrial samples were obtained from 22 healthy, ovulating women undergoing elective surgery. Immunohistochemistry was performed to detect VEGF, Ang1 and Ang2 in endometrial stroma and glands. Semiquantitative evaluation was performed for the three angiogenic factors in the proliferative and secretory phases. The expression of the three parameters was determined by immunohistochemical quantification using specifically developed software. Results: Proteins for VEGF, Ang1 and Ang2 were expressed in the glands as well as in endometrial stroma. In endometrial glands we found a significantly higher expression of the three angiogenetic factors compared to stroma. With respect to the cyclic changes of the endometrium, no significant changes of VEGF and Ang1 were observed in the glands and endometrial stroma. The expression of Ang2 in the glands also remained the same. Compared to the secretory phase of the reproductive cycle, a significantly higher expression of Ang2 was found in endometrial stroma during the proliferative phase. Conclusion: These data indicate a functional role of the angiogenetic factors VEGF, Ang1 and Ang2 and their proangiogenetic effects during the reproductive cycle. Ang1 regulates vascular remodeling and maintenance of vascular integrity, whereas Ang2 acts as an Ang1 antagonist, and provides by the co-expression of VEGF a key de-stabilizing signal involved in initiating neovascularisation. Our results confirm the support of Ang2 in VEGF-regulated angiogenesis during the proliferative phase of the endometrium. In contrast to the proliferative phase a significantly lower expression of Ang2 allows Ang1 to maintain vascular integrity in the secretory phase. Cycle-dependent expression of these angiogenetic growth factors is responsible for the maintenance of the physiological reproductive cycle.

Endometrium - Angiogenese - VEGF - Angiopoetine - Aktivität

Endometrium - angiogenesis - VEGF - angiopoetins - activity

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