Heparin is a promising agent for the treatment of endometriosis-associated fibrosis.
OBJECTIVE
To assess the use of heparin for the medical treatment of endometriosis-associated fibrosis.


METHODS
The effects of heparin on the endometriotic stromal cells (ECSCs)-mediated contractility were investigated.


METHODS
Research laboratory at a medical school.


METHODS
Endometriotic tissues from nine patients were used.


METHODS
Endometriotic stromal cells were cultured three dimensionally in the presence of heparin.


METHODS
The contractility of ECSCs was assessed by collagen gel contraction assay. Heparin-induced morphological changes of ECSCs were evaluated by laser scanning microscopy. The expression of contractility-related molecules in ECSCs was examined by Western blot analysis.


RESULTS
In the presence of 10% fetal bovine serum, treated ECSCs showed significant collagen gel contractility (75.9% decrease in surface area after 48 hour vs. 0 hour controls). Endometriotic stromal cell-mediated gel contraction was significantly attenuated in the presence of heparin in a dose-dependent manner (55.7% reduction of the gel contraction at a concentration of 100 microg/mL of heparin sodium versus untreated controls after 48 hours). Heparin suppressed the ECSC attachment to collagen fibers. The expression of alpha-smooth muscle actin, Ras homology (Rho) A, Rho-associated coiled-coil-forming protein kinase (ROCK)-I, and ROCK-II was down-regulated by heparin administration.


CONCLUSIONS
The present study suggests that heparin is a promising agent for the treatment of endometriosis-associated fibrosis. The inhibition of myofibroblastic differentiation, the attenuation of attachment to collagen fibers, and the suppression of Rho-ROCK-mediated pathway activation in ECSCs are involved in the action mechanisms of heparin.
Nasu
Kaei
K
Department of Obstetrics and Gynecology, Faculty of Medicine, Oita University, Oita, Japan. nasu@med.oita-u.ac.jp
Tsuno
Akitoshi
A
Hirao
Marina
M
Kobayashi
Hironao
H
Yuge
Akitoshi
A
Narahara
Hisashi
H