VEGFR1 Blockade May be Viable Treatment for Women With Endometriosis, Mouse Study Shows

VEGFR1 Blockade May be Viable Treatment for Women With Endometriosis, Mouse Study Shows

Blocking the activity of the vascular endothelial growth factor receptor 1 (VEGFR1) may be a viable treatment for women with endometriosis, a mouse study suggests.

The study, “VEGF Receptor 1-Expressing Macrophages Recruited from Bone Marrow Enhances Angiogenesis in Endometrial Tissues,” was published in Scientific Reports.

Endometriosis, a chronic disease caused by the abnormal growth of womb cells outside the uterus, is a common disorder among women of reproductive age. It is characterized by chronic pelvic pain, infertility, painful sexual intercourse (dyspareunia), painful or irregular menstrual cycles (dysmenorrhea), painful bowel movements (dyschezia), and mental health issues.

The disorder is also closely associated with angiogenesis, that is, the process by which new blood vessels form from preexisting ones. The vascular endothelial growth factor (VEGF) and its receptors are the main players controlling the process of angiogenesis, both in normal and disease conditions.

In this study, a team of Japanese researchers set out to investigate the role of VEGFR1 in angiogenesis associated with endometriosis in a mouse model of disease.

They measured the growth of endometriosis lesions and the density of blood vessels inside these lesions in animals genetically engineered to produce VEGFR1. To trigger endometriosis in the animals, investigators transplanted womb cells from female mice donors into the abdominal wall of other female mice.

Results showed that, in animals lacking VEGFR1, endometriosis lesions grew at a much slower pace than in healthy control mice.

In control animals, lesions normally reached a peak of angiogenesis (measured by the density of blood vessels inside the lesions) approximately 14 days after the transplant; however, in mice unable to produce VEGFR1, lesion growth and the process of angiogenesis were both suppressed 14 days after the induction of endometriosis.

Further analysis showed that endometriosis lesions contained high amounts of cells producing VEGFR1. These cells included mostly macrophages, a type of immune cell responsible for removing dead cells and debris from tissues, which had migrated and infiltrated from the host’s bone marrow into the transplanted endometrial tissues.

In addition, the investigators found these infiltrated macrophages produced and released high amounts of basic fibroblast growth factor (bFGF), stimulating the growth and the formation of new blood vessels inside the lesions.

As expected, when scientists treated animals with Clophosome N, a therapeutic agent that destroys macrophages, they observed a significant reduction in the size of the lesions and blood vessel formation. Similar results were obtained when researchers treated mice with an inhibitor of the FGF receptor and bFGF (PD173047).

“In conclusion, VEGF is a key regulator of growth and angiogenesis in endometrial tissues. Accumulation of VEGFR1-positive macrophages from the host bone marrow was the key driver of growth and angiogenesis in the endometrial implants via secretion [release] of bFGF. Taken together, these results suggest that blocking VEGFR1 with antibodies or a small molecule kinase inhibitor will be a promising strategy for the treatment of endometriosis,” the scientists wrote.

Joana is currently completing her PhD in Biomedicine and Clinical Research at Universidade de Lisboa. She also holds a BSc in Biology and an MSc in Evolutionary and Developmental Biology from Universidade de Lisboa. Her work has been focused on the impact of non-canonical Wnt signaling in the collective behavior of endothelial cells — cells that make up the lining of blood vessels — found in the umbilical cord of newborns.
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Joana is currently completing her PhD in Biomedicine and Clinical Research at Universidade de Lisboa. She also holds a BSc in Biology and an MSc in Evolutionary and Developmental Biology from Universidade de Lisboa. Her work has been focused on the impact of non-canonical Wnt signaling in the collective behavior of endothelial cells — cells that make up the lining of blood vessels — found in the umbilical cord of newborns.
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