Angiopoietin-2 primes infection-induced preterm delivery.
Current knowledge on the participation of angiopoietin-2 (Ang-2) in the inflammatory process and on the importance of bacterial endotoxins (LPS) in the induction of preterm delivery (PTD) led us to investigate the role of Ang-2/LPS interplay in the pathogenesis of PTD. At a first stage, Ang-2 was measured at the end of the first trimester of pregnancy in the serum of 50 women who delivered prematurely; of 88 women well-matched for age and parity who delivered full-term; and of 20 non-pregnant healthy women. Ang-2 was greater in pregnant than in non-pregnant women. The time until delivery was shorter among those with Ang-2 greater than 4 ng/ml (odds ratio for delivery until week 34; p: 0.040). To further investigate the role of Ang-2 for PTD, an experimental model of PTD induced by the intraperitoneal injection of LPS in mice was used. Ang-2 was administered intraperitoneally before LPS on day 14 of pregnancy. When Ang-2 was administered before the LPS diluent, all mice delivered full-term. However, administration of Ang-2 prior LPS accelerated further the time until delivery. Sacrifice experiments showed that the effect of Ang-2 was accompanied by decrease of the penetration of Evans Blue in the embryos and by increase of its penetration in maternal tissues. In parallel, the concentration of tumour necrosis factor-alpha in the maternal circulation, in fetal tissues and in the placentas was significantly decreased. Results indicate that Ang-2 accelerated the phenomena of PTD induced by LPS. This is related with deprivation of fetal perfusion.
3rd Department of Obstetrics and Gynecology, University of Athens, Medical School, Athens, Greece.
Electra N
EN
Polyzou
3rd Department of Obstetrics and Gynecology, University of Athens, Medical School, Athens, Greece.
Nikolaos E
NE
Evangelinakis
4th Department of Internal Medicine, University of Athens, Medical School, Athens, Greece.
Aikaterini
A
Pistiki
4th Department of Internal Medicine, University of Athens, Medical School, Athens, Greece.
Antigone
A
Kotsaki
3rd Department of Obstetrics and Gynecology, University of Athens, Medical School, Athens, Greece.
Charalampos S
CS
Siristatidis
3rd Department of Obstetrics and Gynecology, University of Athens, Medical School, Athens, Greece.
Charalambos G
CG
Chrelias
3rd Department of Obstetrics and Gynecology, University of Athens, Medical School, Athens, Greece.
Emmanuel
E
Salamalekis
3rd Department of Obstetrics and Gynecology, University of Athens, Medical School, Athens, Greece.
Demetrios P
DP
Kassanos
4th Department of Internal Medicine, University of Athens, Medical School, Athens, Greece.
Evangelos J
EJ
Giamarellos-Bourboulis
D042702:Angiopoietin-2 / Q000097:blood* / Q000494:pharmacology*; D000818:Animals; D005260:Female; D005865:Gestational Age; D006801:Humans; D008070:Lipopolysaccharides / Q000009:adverse effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010920:Placenta / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000187:drug effects / Q000378:metabolism; D047928:Premature Birth / Q000097:blood* / Q000139:chemically induced*; D011446:Prospective Studies; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D042702:Angiopoietin-2; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha