Uterine natural killer cells initiate spiral artery remodeling in human pregnancy

Uterine spiral artery remodeling is required for successful human pregnancy; impaired remodeling is associated with pregnancy complications, including late miscarriage, preeclampsia, and fetal growth restriction. The molecular triggers of remodeling are not known, but it is now clear that there are...

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Podrobná bibliografie
Vydáno v:	The FASEB journal Ročník 26; číslo 12; s. 4876
Hlavní autoři:	Robson, Andrew, Harris, Lynda K, Innes, Barbara A, Lash, Gendie E, Aljunaidy, Mais M, Aplin, John D, Baker, Philip N, Robson, Stephen C, Bulmer, Judith N
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States 01.12.2012
Témata:	Angiopoietin-1 - metabolism Angiopoietin-1 - pharmacology Angiopoietin-2 - metabolism Angiopoietin-2 - pharmacology Cell Line Cells, Cultured Culture Media, Conditioned - metabolism Culture Media, Conditioned - pharmacology Decidua - cytology Decidua - metabolism Extracellular Matrix - drug effects Extracellular Matrix - metabolism Female Humans Immunohistochemistry Interferon-gamma - metabolism Interferon-gamma - pharmacology Killer Cells, Natural - metabolism Killer Cells, Natural - physiology Muscle, Smooth, Vascular - cytology Muscle, Smooth, Vascular - metabolism Myocytes, Smooth Muscle - drug effects Myocytes, Smooth Muscle - metabolism Myometrium - cytology Myometrium - metabolism Placenta - cytology Placenta - metabolism Pregnancy Tissue Culture Techniques Trophoblasts - cytology Trophoblasts - metabolism Trophoblasts - physiology Uterine Artery - cytology Uterine Artery - drug effects Uterine Artery - physiology Uterus - blood supply Uterus - cytology Vascular Endothelial Growth Factor C - metabolism Vascular Endothelial Growth Factor C - pharmacology
ISSN:	1530-6860, 1530-6860
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Popis
Shrnutí:	Uterine spiral artery remodeling is required for successful human pregnancy; impaired remodeling is associated with pregnancy complications, including late miscarriage, preeclampsia, and fetal growth restriction. The molecular triggers of remodeling are not known, but it is now clear that there are "trophoblast-independent" and "trophoblast-dependent" stages. Uterine natural killer (uNK) cells are abundant in decidualized endometrium in early pregnancy; they surround spiral arteries and secrete a range of angiogenic growth factors. We hypothesized that uNK cells mediate the initial stages of spiral artery remodeling. uNK cells and extravillous trophoblast (EVT) cells were isolated from early pregnancy decidua and placenta. Chorionic plate arteries from full-term placentas and spiral arteries from nonpregnant myometrium were cultured with angiogenic growth factors or conditioned medium (CM) from uNK cells or EVT or uNK cell/EVT cocultures. In both vessel models, uNK cell CM induced disruption of vascular smooth muscle cells (VSMCs) and breakdown of extracellular matrix components. Angiopoietin (Ang)-1, Ang-2, interferon-γ, and VEGF-C also disrupted VSMC integrity with an Ang-2 inhibitor abrogating the effect of uNK cell CM. These results provide compelling evidence that uNK cells contribute to the early stages of spiral artery remodeling; failure of this process could contribute to pregnancy pathology.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1530-6860 1530-6860
DOI:	10.1096/fj.12-210310