Anti-platelet therapy is efficacious in treating endometriosis induced in mouse

Abstract

In light of recent findings showing that platelets play important roles in the development of endometriosis in general and in fibrogenesis in particular, this study investigated the efficacy of Ozagrel, a TXA synthase inhibitor, in a murine model of endometriosis. In addition, another mouse experiment was conducted to evaluate the effect of timing of platelet depletion and of sequential depletion of platelets and macrophages on the development of endometriosis. It was found that both the Ozagrel treatment and different platelet depletion schemes resulted in significant reduction in lesion growth (all P-values <0.01) along with improved hyperalgesia in mice with induced endometriosis. They also significantly reduced the expression of markers of proliferation, angiogenesis, inflammation and fibrosis as well as decreased macrophage infiltration in endometriotic lesions (all P-values <0.05). Compared with untreated mice, pre-emptive depletion of platelets as well as platelet depletion after induction resulted in significant reduction in lesion weight (both P-values <0.001), while sequential depletion of platelets and macrophages yielded similar reduction. These results, in conjunction with other roles that platelets play in the development of endometriosis, strongly argue for the potential of anti-platelet therapy in treating endometriosis.

Further Evidence for Hypercoagulability in Women With Ovarian Endometriomas

“…35 Finally, the hypercoagulability seemingly resulting from endometriosis suggests that anticoagulation or antiplatelet therapy could be promising as already shown in animal models of endometriosis. 15,16,25 Although our study did not replicate our previous finding that aPTT is shortened in women with endometriosis, 19 we were able to replicate other findings reported previously, that is, shortened TT, elevated plasma fibrinogen levels, and increased platelet activation rate. 19 In addition, we replicated our previous finding that the platelet activation rate was significantly reduced after surgical removal of endometriotic lesions.…”

“…13 In the last few years, we have provided many pieces of evidence that platelets play important roles in the development of endometriosis. [14][15][16][17][18] We have also provided evidence that women with endometriosis appear to be in a hypercoagulable state as manifested by shortened thrombin time (TT) and activated partial thromboplastin time (aPTT) but similar prothrombin time (PT), platelet count, and international normalized ratio (INR) to those without endometriosis, suggestive of the activation of the intrinsic, but not extrinsic, coagulation pathway. 19 In addition, women with endometriosis had increased plasma levels of fibrinogen and platelet activation rate.…”

Pathogenesis of deep endometriosis

“…The many immunologic disturbances were recently reviewed (92)(93)(94)(95)(96)(97)(98)(99). Specific attention was given to natural killer cells (95,100) and recently to the role of platelets in their function (101,102). The natural killer activity is decreased in PF and in plasma of women with endometriosis (103)(104)(105) and after excision of deep endometriosis their activity remains low, whereas elevated CA-125 concentrations return to normal (106).…”

Platelets induce increased estrogen production through NF-κB and TGF-β1 signaling pathways in endometriotic stromal cells

“…List of primary antibodies for western blot analysis used in this study. 4, ..., 10 and 12), starting from 2 days before the induction of endometriosis (day 0, the day when induction was performed) 95 . Two days after the first injection, endometriosis was induced as described above for all mice.…”