Angiopoietin-2 primes infection-induced preterm delivery

• Published in: PloS one Vol. 9; no. 1; p. e86523
• Main Authors: Polyzou, Electra N, Evangelinakis, Nikolaos E, Pistiki, Aikaterini, Kotsaki, Antigone, Siristatidis, Charalampos S, Chrelias, Charalambos G, Salamalekis, Emmanuel, Kassanos, Demetrios P, Giamarellos-Bourboulis, Evangelos J
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 21.01.2014; Public Library of Science (PLoS)
• Subjects: Age; Angiogenesis; Angiopoietin; Angiopoietin-2 - blood; Angiopoietin-2 - pharmacology; Animal tissues; Animals; Bacteria; Bacterial infections; Biology; Childbirth & labor; Cytomegalovirus; Deprivation; Embryos; Endotoxins; Female; Fetuses; Gestational Age; Gynecology; Health aspects; Hepatitis; Humans; Hypotheses; Infections; Inflammation; Internal medicine; Lipopolysaccharides; Lipopolysaccharides - adverse effects; Male; Medical schools; Medicine; Mice; Mice, Inbred C57BL; Obstetrics; Pathogenesis; Penetration; Perfusion; Placenta - drug effects; Placenta - metabolism; Pregnancy; Pregnancy Trimester, First - drug effects; Pregnancy Trimester, First - metabolism; Pregnant women; Premature birth; Premature Birth - blood; Premature Birth - chemically induced; Prospective Studies; Pseudomonas aeruginosa; Rodents; TNF inhibitors; Tumor necrosis factor; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-TNF; Tumors; Women's health; Womens health; Greece; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0086523

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.