title: hCG stimulates angiogenic signals in lymphatic endothelial and circulating angiogenic cells.
abstract: Human chorionic gonadotropin (hCG) has long been associated with the initiation and maintenance of pregnancy, where angiogenesis plays an important role. However, the function of hCG in angiogenesis and the recruitment of vascular active cells are not fully understood. In this study, the role of hCG and its receptor in circulating angiogenic and human endothelial cells, including lymphatic, uterine microvascular, and umbilical vein endothelial cells, was examined. Immunohistochemistry and immunoblot analysis were used to detect LH/hCG receptor expression and the expression of hCG-induced angiogenic molecules. HIF-1α was determined via ELISA and downstream molecules, such as CXCL12 and CXCR4, via real-time PCR. Chemotaxis was analyzed using Boyden chambers. Our results show that the LH/hCG receptor was present in all tested cells. Furthermore, hCG was able to stimulate LH/hCG-receptor-specific migration in a dose-dependent fashion and induce key angiogenic molecules, including HIF-1α, CXCL12, and CXCR4. In conclusion, our findings underscore the importance of hCG as one of the first angiogenic molecules produced by the conceptus. hCG itself alters endothelial motility, recruitment, and expression of pro-angiogenic molecules and may therefore play an important role in vascular adaption during implantation and early placental formation.
authors.affiliation: University Düsseldorf, Medical Faculty, Department of Obstetrics, Gynecology and REI (UniKiD), Moorenstrasse 5, 40225 Düsseldorf, Germany. Electronic address: Schanz@unikid.de.
authors.forename: Andrea
authors.initials: A
authors.lastname: Schanz
authors.affiliation: University Düsseldorf, Medical Faculty, Division of Cardiology, Pulmonology, and Vascular Medicine, Moorenstrasse 5, 40225 Düsseldorf, Germany(1). Electronic address: Margarete.Lukosz@med.uni-duesseldorf.de.
authors.forename: Margarete
authors.initials: M
authors.lastname: Lukosz
authors.affiliation: University Düsseldorf, Medical Faculty, Department of Obstetrics, Gynecology and REI (UniKiD), Moorenstrasse 5, 40225 Düsseldorf, Germany. Electronic address: Hess@unikid.de.
authors.forename: Alexandra P
authors.initials: AP
authors.lastname: Hess
authors.affiliation: University Düsseldorf, Medical Faculty, Department of Obstetrics, Gynecology and REI (UniKiD), Moorenstrasse 5, 40225 Düsseldorf, Germany. Electronic address: Baston-Buest@unikid.de.
authors.forename: Dunja M
authors.initials: DM
authors.lastname: Baston-Büst
authors.affiliation: University Düsseldorf, Medical Faculty, Department of Obstetrics, Gynecology and REI (UniKiD), Moorenstrasse 5, 40225 Düsseldorf, Germany. Electronic address: Kruessel@unikid.de.
authors.forename: Jan S
authors.initials: JS
authors.lastname: Krüssel
authors.affiliation: University Düsseldorf, Medical Faculty, Division of Cardiology, Pulmonology, and Vascular Medicine, Moorenstrasse 5, 40225 Düsseldorf, Germany(1); Department of Cardiology, University of California San Francisco, 505 Parnassus Avenue, San Francisco, CA 94143, USA(2). Electronic address: Christian.Heiss@med.uni-duesseldorf.de.
authors.forename: Christian
authors.initials: C
authors.lastname: Heiss
mesh_terms: D002465:Cell Movement / Q000187:drug effects* / Q000276:immunology; D054377:Chemokine CXCL12 / Q000276:immunology; D006063:Chorionic Gonadotropin / Q000276:immunology / Q000494:pharmacology*; D042783:Endothelial Cells / Q000166:cytology / Q000276:immunology*; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000276:immunology; D011247:Pregnancy; D019718:Receptors, CXCR4 / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects* / Q000276:immunology
chemical_list: C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D006063:Chorionic Gonadotropin; D019718:Receptors, CXCR4
keywords: Angiogenesis; Circulating angiogenic cells; Human chorionic gonadotropin; Lymphatic endothelial cells; hCG