Kisspeptin-10 Inhibits Angiogenesis in Human Placental Vessels ex Vivo and Endothelial Cells in Vitro

• Published in: Endocrinology (Philadelphia) 2010-12, Vol.151 (12), p.5927-5934
• Main Authors: Ramaesh, Thayalini, Logie, James J, Roseweir, Antonia K, Millar, Robert P, Walker, Brian R, Hadoke, Patrick W. F, Reynolds, Rebecca M
• Format: Article
• Language: English
• Subjects: Angiogenesis; Apoptosis; Arteries; Biological activity; Biological and medical sciences; Blood vessels; Cell Survival; Dose-Response Relationship, Drug; Endothelial cells; Endothelial Cells - drug effects; Female; Fundamental and applied biological sciences. Psychology; Humans; Kiss1 protein; Kisspeptins; Metastases; Neovascularization, Physiologic - drug effects; Pituitary (anterior); Placenta; Placenta - blood supply; Pregnancy; Receptors; Reproductive system; Tumor Suppressor Proteins - pharmacology; Umbilical vein; Vasoconstriction; Vertebrates: endocrinology
• ISSN: 0013-7227; 1945-7170
• DOI: 10.1210/en.2010-0565

Recent studies suggest that kisspeptin (a neuropeptide central to the regulation of gonadotrophin secretion) has diverse roles in human physiology, including a putative role in implantation and placental function. Kisspeptin and its receptor are present in human blood vessels, where they mediate vasoconstriction, and kisspeptin is known to inhibit tumor metastasis and trophoblast invasion, both processes involving angiogenesis. We hypothesized that kisspeptin contributes to the regulation of angiogenesis in the reproductive system. The presence of the kisspeptin receptor was confirmed in human placental blood vessels and human umbilical vein endothelial cells (HUVEC) using immunochemistry. The ability of kisspeptin-10 (KP-10) (a shorter biologically active processed peptide) to inhibit angiogenesis was tested in explanted human placental arteries and HUVEC using complementary ex vivo and in vitro assays. KP-10 inhibited new vessel sprouting from placental arteries embedded in Matrigel and tube-like structure formation by HUVEC, in a concentration-dependent manner. KP-10 had no effect on HUVEC viability or apoptosis but induced concentration-dependent inhibition of proliferation and migration. In conclusion, KP-10 has antiangiogenic effects and, given its high expression in the placenta, may contribute to the regulation of angiogenesis in this tissue. Kisspeptin has antiangiogenic effects, including in placental vessels; given its high levels in placenta, kisspeptin may regulate placental angiogenesis, a key process in successful placentation.