Formation of New Blood Vessels Accompanies Progression of Ovarian Endometriosis

Formation of New Blood Vessels Accompanies Progression of Ovarian Endometriosis

Ovarian endometriosis is associated with increased levels of molecular factors that stimulate the pathological formation of new blood vessels that support the endometriomas, according to a new study.

The study, “Regulation of Matrix Metalloproteinase-2 Activity by COX-2-PGE2-pAKT Axis Promotes Angiogenesis in Endometriosis,” was published in the journal PLoS One.

Endometriosis is characterized by the presence of viable endometrial glands and stroma outside of the uterus that can grow and bleed cyclically, frequently leading to pelvic inflammation, adhesion, chronic pain, and infertility. These new endometriotic growths are supported by angiogenesis — the formation of new blood vessels from a pre-existing blood vessel.

To understand exactly which molecules are at play during pathological angiogenesis, researchers collected blood and endometrium samples from 73 women with endometriosis and 15 healthy women. They then analyzed the levels of several proteins known to participate in the formation of blood vessels, such as MMP-2, VEGF, VEGF receptor-2, COX-2, and von Willebrand factor, and correlated these with angiogenesis during the progression of endometriosis.

Women with endometriosis had reduced MMP-2 activity in normal endometrium compared to healthy women, but higher levels of this protein in samples of endometriotic growths. Levels of MMP-2 activity increased significantly with disease severity. Consistent with these findings, the molecular inhibitors of MMP-2 were found to be decreased in later stages of endometriosis, whereas levels of the PGE-2 protein, which activates MMP-2, were increased.

This imbalance in the proteins that control MMP-2 contributed to the abnormal activity of this protein, leading to endometriosis.

Levels of VEGF, VEGF receptor-2, COX-2, and von Willebrand factor were significantly increased with the advancement of the disease, confirming the involvement of angiogenesis during ovarian endometriosis progression.

Experiments in a culture dish showed that inhibition of COX-2 or specific chemical inhibition of MMP-2 significantly reduced MMP-2 activity, blood vessel formation, and lesion numbers.

“Ovarian endometriosis is associated with increased MMP-2 activity and pathological angiogenesis,” the authors wrote. “MMP-2 is involved in cellular migration and invasion, thus selective inhibition of MMP-2 activity significantly impedes [blood vessel] formation as well as angiogenesis. Our data suggest the role of MMP-2 through PGE2-mediated pathway for the promotion of angiogenesis in endometriosis.”

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