Low molecular weight heparin modulates maternal immune response in pregnant women and mice with thrombophilia.
Autor: | Luley L; Experimental Obstetrics and Gynecology, Medical Faculty, Otto-von-Guericke-University, Magdeburg, Germany; Department of Gynecology and Obstetrics, Medical Faculty, Otto-von-Guericke-University, Magdeburg, Germany., Schumacher A, Mulla MJ, Franke D, Löttge M, Fill Malfertheiner S, Tchaikovski SN, Costa SD, Hoppe B, Abrahams VM, Zenclussen AC |
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Jazyk: | angličtina |
Zdroj: | American journal of reproductive immunology (New York, N.Y. : 1989) [Am J Reprod Immunol] 2015 May; Vol. 73 (5), pp. 417-27. Date of Electronic Publication: 2014 Dec 11. |
DOI: | 10.1111/aji.12348 |
Abstrakt: | Problem: Thrombophilia is associated with pregnancy complications. Treatment with low molecular weight heparin (LMWH) improves pregnancy outcome, but the underlying mechanisms are not clear. Methods of Study: We analyzed Treg frequency in blood from thrombophilic pregnancies treated with LMWH (n = 32) or untreated (n = 33) and from healthy pregnancies (n = 39) at all trimesters. Additionally, we treated pregnant wild-type, heterozygous and homozygous factor-V-Leiden (FVL) mice with LMWH or PBS and determined Treg frequency, pro-/anti-inflammatory cytokine levels and Caspase-3-activity in placenta and decidua. Results: Treg frequencies were increased in second and third trimester in LMWH-treated thrombophilic pregnancies compared to controls. Treg levels were comparable to those of normal pregnancies. Homozygous FVL mice had decreased decidual Tregs compared to wild-type mice. LMWH treatment normalized Tregs and was associated with increased decidual IL-10 mRNA. LMWH diminished Caspase-3-activity in mice of all genotypes. Conclusion: We demonstrated anti-apoptotic and anti-inflammatory effects of LMWH in pregnant FVL mice. LMWH increased Treg levels in mice and humans, which suggests benefits of LMWH treatment for thrombophilic women during pregnancy. (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.) |
Databáze: | MEDLINE |
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