Angiogenesis, the process of new vessels sprouting from the existing vasculature, is a
critical process during early development. However, angiogenesis rarely occurs in the
adult, except in response to cyclic hormonal stimulation in the ovary and uterus, in
response to injury, and in response to pathological conditions such as tumorigenesis
and diabetes mellitus.
The TEK receptor tyrosine kinase is expressed almost exclusively in endothelial cells in mice, rats, and humans. This receptor
possesses a unique extracellular domain containing 2 immunoglobulin-like loops separated by 3 epidermal growth factor-like
repeats that are connected to 3 fibronectin type III-like repeats. The complex extracellular domain and the fact that the
expression of this receptor tyrosine kinase is restricted to the endothelial cell lineage suggest that TEK plays a unique role
within this cell lineage. The ligand for the receptor is
angiopoietin-1.
NCBI Summary:
The TEK receptor tyrosine kinase is expressed almost exclusively in endothelial cells in mice, rats, and humans. This receptor possesses a unique extracellular domain containing 2 immunoglobulin-like loops separated by 3 epidermal growth factor-like repeats that are connected to 3 fibronectin type III-like repeats. The ligand for the receptor is angiopoietin-1. Defects in TEK are associated with inherited venous malformations; the TEK signaling pathway appears to be critical for endothelial cell-smooth muscle cell communication in venous morphogenesis. TEK is closely related to the TIE receptor tyrosine kinase.
General function
Receptor
Comment
Cellular localization
Plasma membrane
Comment
Ovarian function
Luteinization
Comment
Angiopoietins/TIE2 System and VEGF Are Involved in Ovarian Function in a DHEA Rat Model of Polycystic Ovary Syndrome. Abramovich D et al. Polycystic ovary syndrome (PCOS) is the most common endocrinological pathology among women of reproductive age. It is characterized by anovulation, oligo- or amenorrhea, hyperandrogenism, obesity, and insulin resistance. PCOS patients present with elevated levels of vascular endothelial growth factor (VEGF) in serum and follicular fluid. In this study, we examined the ovarian expression of angiopoietins (ANGPT) and their receptor tyrosine kinase receptor (TIE2), involved in the stabilization of blood vessels, in a rat model of dehydroepiandrosterone-induced PCOS. We also analyzed the effect of ovarian VEGF inhibition on ANGPT/TIE2, follicular development, and vascular stability. VEGF levels were increased in the PCOS ovaries, whereas the levels of its receptor fetal liver kinase-1 were decreased. In addition, the periendothelial cell area and the ANGPT1 to ANGPT2 ratio in the ovary were increased in the PCOS group. Percentage of primary follicles was increased and the percentage of preantral follicles and corpora lutea was decreased in the PCOS group. VEGF inhibition decreased the percentage of primary follicles close to control values. Interestingly, despite the presence of cysts in the ovaries from VEGF inhibitor-treated PCOS rats, its percentage was lower than the PCOS group without treatment. In summary, this study describes an alteration not only in the VEGF/fetal liver kinase-1 system but also in the ANGPT/TIE2 system in a dehydroepiandrosterone-induced PCOS rat model. This leads to an increase in periendothelial cell recruitment. We also demonstrated that ovarian VEGF inhibition can partially restore the accumulation of small follicles in PCOS rats and reduces cyst formation, improving ovulation and follicular development. Therefore, the inhibition of VEGF could be considered, in addition to other currently applied treatments, as a new strategy to be studied in PCOS patients to restore ovarian function.
Expression regulated by
Comment
Circulating levels of total angiopoietin-2 and the soluble Tie-2 receptor in women during ovarian stimulation and early gestation. Molskness TA et al. Circulating levels of Ang-2 and sTie-2 receptor were detectable but invariant in women during COS cycles. During the postimplantation period, the rise in Ang-2 (but not sTie-2) levels probably reflects placental rather than luteal production.
Ovarian localization
Luteal cells
Comment
Wong AL et al reported that Tie2
expression was localized by immunohistochemistry to the endothelium of neovessels in rat tissues undergoing angiogenesis during hormonally stimulated follicular maturation
and uterine development and in healing skin wounds.
Hata K et al 2000 reported the expression of TP and TIE2 genes in normal ovary with corpus
luteum and in ovarian cancer.
Follicle stages
Corpus luteum
Comment
Phenotypes
Mutations
2 mutations
Species: mouse
Mutation name: None
type: null mutation fertility: embryonic lethal Comment: Tie2 knockout mice die by embryonic day
10.5 with specific defects in the formation of microvessels due to deficiency of the endothelium Puri MC, et al 1999 .
Species: human
Mutation name: None
type: naturally occurring fertility: fertile Comment:Vikkula et al. (1996) identified a missense arg849-to-trp mutation in the kinase
domain of TIE2 segregating with dominantly inherited venous malformations. Using proteins expressed in
insect cells, they demonstrated that the mutation resulted in increased activity of TIE2. They concluded that activating mutation
in TIE2 caused inherited venous malformations in the 2 families and that the TIE2 signaling pathway is critical for endothelial
cell-smooth muscle cell communication in venous morphogenesis.