Antiphospholipid antibodies affect human endometrial angiogenesis.
Antiphospholipid antibodies (aPL) represent an important risk factor for thrombosis and recurrent miscarriage in patients with antiphospholipid syndrome (APS). The mechanisms of aPL-mediated pregnancy failure have been researched. Previous studies demonstrated that aPL bind trophoblast cells, reducing proliferation, human chorionic gonadotrophin release, and in vitro invasiveness. Recent data suggest that aPL are also able to react with human decidual cells, inducing a proinflammatory phenotype. Decidua, a newly formed tissue on the maternal side of the human placenta, is characterized by active angiogenesis and structural modifications of the spiral arteries in early pregnancy. Since angiogenesis is a critical component of normal placentation, the purpose of our study was to evaluate the role of aPL on human endometrial angiogenesis. For this reason, we investigated the effect of aPL on in vitro endometrial endothelial cell (HEEC) angiogenesis, VEGF secretion by ELISA, matrix metalloproteinases (MMPs) activity by gelatin zymography, and DNA binding activity of NFKB by a sensitive multiwell colorimetric assay. Furthermore, we performed experiments to study whether aPL affects in vivo angiogenesis in a murine model. We found that aPL significantly decrease the number and the total length of the tubules formed by HEEC on in vitro Matrigel assay and reduce newly formed vessels in aPL-inoculated mice. Moreover, aPL reduce significantly both VEGF and MMPs production and, at the nuclear level, NFKB DNA binding activity. From our results, it appears that aPL are associated with an inhibition of angiogenesis, suggesting further additional mechanisms to explain the defective placentation in the APS.
Di Simone
Nicoletta
N
Department of Obstetrics and Gynecology, Catholic University of Sacred Heart, Rome, Italy. nicolettadisimone@rm.unicatt.it
Di Nicuolo
Fiorella
F
D'Ippolito
Silvia
S
Castellani
Roberta
R
Tersigni
Chiara
C
Caruso
Alessandro
A
Meroni
Pierluigi
P
Marana
Riccardo
R
D000026:Abortion, Habitual / Q000209:etiology; D000328:Adult; D000818:Animals; D017152:Antibodies, Antiphospholipid / Q000378:metabolism / Q000494:pharmacology*; D016736:Antiphospholipid Syndrome / Q000150:complications; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D004717:Endometrium / Q000098:blood supply* / Q000276:immunology / Q000378:metabolism; D042783:Endothelial Cells / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology*; D011247:Pregnancy; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D017152:Antibodies, Antiphospholipid; D061965:Matrix Metalloproteinase Inhibitors; D016328:NF-kappa B; D042461:Vascular Endothelial Growth Factor A; D004247:DNA; D020782:Matrix Metalloproteinases