Regulation of endometrial vascular remodelling: role of the vascular endothelial growth factor family and the angiopoietin–TIE signalling system

Abstract

Angiogenesis, lymphangiogenesis and vascular maturation occur on a regular, physiological basis in human endometrium. These processes form part of a continuum of vascular remodelling involving numerous regulatory factors. Key factors include vascular endothelial growth factor (VEGF)A, VEGFC and VEGFD, and their associated receptors VEGFR1, VEGFR2 and VEGFR3. A second group of vascular regulatory proteins belongs to the angiopoietin (ANG)-TIE system. Although members of the VEGF family and the ANG-TIE system are represented in the endometrium, our understanding of how these different molecules interact to regulate remodelling of the blood and lymphatic vasculature present in the endometrium is still limited. A review of the current information is provided.

Vascular endothelial growth factor-A isoform and (co)receptor expression are differentially regulated by 17β-oestradiol in the ovariectomised mouse uterus

“…Angiogenesis (the growth of new microvessels from preexisting vasculature) occurs as part of the cyclic growth and development of the endometrium , 2009. A key hormone in this cyclicity is the ovarian steroid 17b-oestradiol (E 2 ), which is responsible for the rapid growth and proliferation of endometrial tissue that occurs during the proliferative stage of the human menstrual cycle.…”

Pien Tze Huang suppresses VEGF-C-mediated lymphangiogenesis in colorectal cancer

“…VEGF-C, a lymphangiogenic growth factor, is a key regulator of lymphangiogenesis and tumor metastasis (24). Early studies have suggested that VEGF-C can promote the growth of new LVs and regional metastasis by binding to their receptor tyrosine kinase VEGFR-3, which was found to be densely expressed in lymphatic endothelial cells (25,26). Studies with human or animal tumor models have demonstrated that malignant tumor cells themselves can secrete high levels of VEGF-C (27), and this overexpression of tumor-derived VEGF-C may play an important role in the occurrence of intratumoral lymphangiogenesis leading to the dissemination of tumor cells to regional lymph nodes (28)(29)(30).…”

Stimulated mast cells promote maturation of myocardial microvascular endothelial cell neovessels by modulating the angiopoietin-Tie-2 signaling pathway

“…It has been shown that Ang-1 is an agonist for endothelial cells and that Ang-2 can act as a context-dependent antagonist (21). Studies demonstrated that Ang-1 is essential for vascular development by promoting blood vessel maturation (9), and by inhibiting vessel leakage, endothelial apoptosis, and microvascular regression (22). Consistent with these in vivo studies, Ang-1 promotes monolayer integrity in cultured endothelial cells (23).…”

“…While VEGF is required to initiate neovessel formation, Ang is needed for neovessel maturation (6,7). Interestingly, studies showed an antagonistic regulation between Ang-1 and Ang-2, the two key ligands for Tie-2 receptor (known as the endothelial-specific receptor tyrosine kinase), and that they are involved in vascular formation and maturation (8,9). Interrupting Ang/Tie-2 signaling has been shown to impede vascular maturation and to disrupt vessel formation.…”