VEGF and nitric oxide synthase immunoexpression in Down's syndrome amniotic fluid stem cells.
BACKGROUND
It has been previously observed that the amniotic fluid obtained from Down's syndrome (DS) pregnancies showed lower levels of vascular endothelial growth factor (VEGF) and higher levels of nitric oxide (NO) with respect to the controls, suggesting the presence of an imbalance between placental vascularization and altered endothelial function. The aim of our study was to evaluate the immunohistochemical expression and localization of VEGF and nitric oxide synthase (NOS) isoforms in cultured amniotic fluid mesenchymal stem cells (AF-MSCs) isolated from normal euploid pregnancies and pregnancies complicated by trisomy 21. In addition, we measured the VEGF and NO content in cell culture supernatants to analyse their production by AF-MSCs.


METHODS
AF-MSCs were obtained from women with foetal DS and controls matched for age and gestation, and expanded in culture. The cells were then evaluated for the immunohistochemical expression of VEGF and NOS isoforms, as well as for the release of VEGF and NO.


RESULTS
Our analyses showed that both the VEGF expression and production were significantly lower in DS-AF-MSCs with respect to the controls. As regards NOS, immunohistochemical expression of eNOS was significantly reduced in DS-AF-MSCs, whereas the nNOS and iNOS were similarly immunoexpressed in both groups of cells. Moreover, we observed that the NO content was significantly higher in medium derived by DS-AF-MSCs.


CONCLUSIONS
Our study shows, for the first time, the differences between AF-MSCs isolated from control and trisomy 21 pregnancies and suggest an involvement of NO and VEGF in the physiopathological mechanisms associated with DS pregnancy.
Salvolini
Eleonora
E
Department of Molecular Pathology and Innovative Therapies - Histology Section, Polytechnic University of Marche, Ancona, Italy. e.salvolini@univpm.it
Orciani
Monia
M
Lucarini
Guendalina
G
Vignini
Arianna
A
Tranquilli
Andrea Luigi
AL
Di Primio
Roberto
R
D000653:Amniotic Fluid / Q000378:metabolism*; D016022:Case-Control Studies; D004314:Down Syndrome / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D011247:Pregnancy; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D042461:Vascular Endothelial Growth Factor A; D019001:Nitric Oxide Synthase