Vascular disrupting effects of combretastatin A4 phosphate on murine endometriotic lesions

Capsule:
This study demonstrates for the first time a selective vascular disrupting effect of CA4P on endometriotic lesions, indicating that vascular disrupting agents may be suitable for the therapy of endometriosis.

Authors:
Dilu Feng, M.D., Michael D. Menger, M.D., Matthias W. Laschke, M.D., Ph.D.

Volume 100, Issue 5, Pages 1459-1467.e1, November 2013

Abstract:

Objective:
To study the effect of combretastatin A4 phosphate (CA4P) on the vascularization of endometriotic lesions.

Design:
Intravital microscopic, histologic, and immunohistochemical study.

Setting:
University institute.

Animal(s):
BALB/c mice.

Intervention(s):
Murine endometriotic lesions were induced by syngeneic transplantation of endometrium into dorsal skinfold chambers. After 6 days, the mice received an intraperitoneal injection of 80 mg/kg CA4P or vehicle.

Main Outcome Measure(s):
Vascularization of the lesions and the surrounding tissue was analyzed by intravital fluorescence microscopy over 8 days. Lesion morphology, vessel maturation, viability, and proliferation of endometrial glands and stroma were assessed by histology and immunohistochemistry.

Result(s):
All lesions were initially well vascularized, containing immature and mature microvessels. Injection of CA4P induced a selective vessel collapse in the lesions without affecting the surrounding microvasculature. This resulted in a decreased functional capillary density and blood perfusion of CA4P-treated lesions after 2 hours when compared with controls. However, the vascularization of the lesions progressively normalized, and their numbers of proliferating and apoptotic cells did not differ from those of controls.

Conclusion(s):
This study demonstrates a selective vascular disrupting effect of CA4P on endometriotic lesions, indicating that vascular disrupting agents may be suitable for endometriosis therapy.

Translate »