|
Academic/Biomedical Research
News & Jobs
|
|
|
|
|
|
|
|
|
|
|
|
|
Free Newsletters
Archive
My Subscriptions
News by Subject
News by Disease
News by Date
PLoS
Search News
Post Your News
JoVE
Job Seeker Login
Most Recent Jobs
Search Jobs
Post Resume
Career Fairs
Career Resources
For Employers
Regional News
US & Canada
Biotech Bay
Biotech Beach
Genetown
Pharm Country
BioCapital
BioMidwest
Bio NC
BioForest
Southern Pharm
BioCanada East
US Device
Europe
Asia
Company Profiles
Research Store
Research Events
Post an Event
Real Estate
Business Opportunities
|
|
|
|
PLoS By Category | Recent
PLoS Articles
|
|
Immunology - Molecular Biology - Obstetrics - Women's Health
|
Effect of Low Molecular Weight Heparins (LMWHs) on antiphospholipid Antibodies (aPL) – Mediated Inhibition of Endometrial Angiogenesis
Published:
Tuesday, January 03, 2012
Author:
Silvia D'Ippolito et al.
by Silvia D'Ippolito, Riccardo Marana, Fiorella Di Nicuolo, Roberta Castellani, Manuela Veglia, John Stinson, Giovanni Scambia, Nicoletta Di Simone
Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by vascular thrombosis and/or pregnancy morbidity in the presence of circulating antiphospholipid antibodies (aPL). Different pathogenic mechanisms for aPL-mediated pregnancy failure have been proposed. In particular a direct effect of aPL on both maternal and fetal side of the placental tissue has been reported, since their reactivity with ß2-glycoprotein I (ß2GPI) makes them adhere to trophoblast and human endometrial endothelial cell (HEEC) membranes. ß2GPI can be recognized by aPL that, once bound, interfere with both trophoblast functions and with the HEEC differentiation.
APS patients can be successfully treated with Low Molecular Weight Heparin (LMWH). Recent reports suggest that LMWH acts through mechanisms alternative to its well known anticoagulant effect, because of its ability to bind ß2GPI. In our previous studies, we showed that LMWH is able to reduce the aPL binding to trophoblasts and restore cell invasiveness and differentiation. So far, however, no study has described its effects on endometrial angiogenesis.
The aim of our research was to evaluate whether two LMWHs, tinzaparin and enoxaparin, have an effect on the aPL-inhibited endometrial angiogenesis. This prompted us to investigate: (i) in vitro HEEC angiogenesis through a Matrigel assay; (ii) VEGF secretion by ELISA; (iii) matrix metalloproteinase-2 (MMP-2) activity by gelatin zymography; (iv) Nuclear Factor-?B (NF-?B) DNA binding activity by colorimetric assay; (v) STAT-3 activation by a sandwich-ELISA kit. Furthermore, using an in vivo murine model we investigated the LMWHs effects on angiogenesis.
We demonstrated that the addition of LMWHs prevents aPL-inhibited HEEC angiogenesis, both in vitro and in vivo, and is able to restore the aPL inhibited NF-?B and/or STAT-3 activity, the VEGF secretion and the MMPs activity.
The demonstration of a beneficial role for LMWHs on the aPL-inhibited HEEC angiogenesis might provide additional mechanisms whereby this treatment protects early pregnancy in APS.
More...
|
|
|
 |
|
|
|
|
|
|
|
|