Effects of low molecular weight heparin and heparin-binding epidermal growth factor on human trophoblast in first trimester

Chen, Ying; Wu, Xiaoxia; Tan, Jiewen; Liu, Mei‐Lan; Liu, Yinglin; Zhang, Jianping

doi:10.1016/j.fertnstert.2011.12.002

Cited by 23 publications

(18 citation statements)

References 31 publications

(31 reference statements)

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“…The recent realization that LMWH, like unfractionated heparin (UFH), also risks thrombocytopenia, and UFH better prevents complement activation prompts some investigators to prefer UFH to LMWH [42]. There are, however, other recent reports that claim better safety profile of LMWH with reference to incidence of thrombocytopenia [45] and cytoprotection [46]. These issues will perhaps be resolved once more data are generated through controlled studies.…”

Section: Discussionmentioning

confidence: 99%

Aspirin and Low-Molecular Weight Heparin Combination Therapy Effectively Prevents Recurrent Miscarriage in Hyperhomocysteinemic Women

et al. 2013

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The management of recurrent pregnancy loss (RPL) still remains a great challenge, and women with polycystic ovarian syndrome (PCOS) are at a greater risk for spontaneous abortion. Treatment with low-molecular-weight heparin (LMWH) has become an accepted treatment option for women with RPL; however, the subgroup of women, who are likely to respond to LMWH, has not been precisely identified. The present study evaluated the efficacy of LMWH with reference to PCOS and associated metabolic phenotypes including hyperhomocysteinemia (HHcy), insulin resistance (IR) and obesity. This prospective observational study was conducted at Institute of Reproductive Medicine, Kolkata, India. A total of 967 women with history of 2 or more consecutive first trimester abortions were screened and 336 were selected for the study. The selected patients were initially divided on the basis of presence or absence of PCOS, while subsequent stratification was based on HHcy, IR and/or obesity. The subjects had treatment with aspirin during one conception cycle and aspirin-LMWH combined anticoagulant therapy for the immediate next conception cycle, if the first treated cycle was unsuccessful. Pregnancy salvage was the sole outcome measure. The overall rate of pregnancy salvage following aspirin therapy was 43.15%, which was mostly represented by normohomocysteinemic women, while the salvage rate was lower in the HHcy populations irrespective of the presence or absence of PCOS, IR, or obesity. By contrast, aspirin-LMWH combined therapy could rescue 66.84% pregnancies in the aspirin-failed cases. Logistic regression analyses showed that HHcy remained a significant factor in predicting salvage rates in the PCOS, IR, and obese subpopulations controlled for other confounding factors. With regard to pregnancy salvage, combined anticoagulant therapy with aspirin and LMWH conferred added benefit to those with HHcy phenotype.

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Section: Discussionmentioning

confidence: 99%

Aspirin and Low-Molecular Weight Heparin Combination Therapy Effectively Prevents Recurrent Miscarriage in Hyperhomocysteinemic Women

et al. 2013

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“…Besides preparing both the preimplantation embryo and uterus for their mutual interaction (39,40), HB-EGF facilitates directly the process of implantation by inducing trophoblast differentiation, invasive phenotype, and motility (29,41,42). Previous research reported an increased invasion rate in first trimester EVTC after treatment with recombinant HB-EGF (29,40,42) as well as an impaired HB-EGF expression and signaling in placentas from pregnancies complicated with preeclampsia (43), small for gestational age fetuses, and APS, all conditions associated with decreased trophoblast invasion (44) and increased levels of trophoblast apoptosis (45,46).…”

Section: Discussionmentioning

confidence: 99%

“…After being synthesized as a transmembrane protein (pro-HB-EGF), it can be cleaved, through the shedding activity of MMPs, at the plasma membrane to yield soluble HB-EGF (sHB-EGF), which represents a stronger mitogenic molecule stimulating cell growth rate, migration, and colony-forming ability. HB-EGF is expressed in endometrial tissue and in first trimester human placenta, within the VTC, the EVTC, and the basal plate, predominantly at the sites of EVTC invasion (27), where it directly facilitates the process of implantation by stimulating trophoblast differentiation, invasive phenotype, and motility (28,29).…”

mentioning

confidence: 99%

Emerging nonanticoagulant role of low molecular weight heparins on extravillous trophoblast functions and on heparin binding–epidermal growth factor and cystein-rich angiogenic inducer 61 expression

D’Ippolito

Nicuolo

Marana

et al. 2012

Fertility and Sterility

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“…Interestingly, in a rat mesentery angiogenesis assay, dalteparin significantly stimulated angiogenesis in an inversely dose-dependent manner at therapeutically relevant levels, ranging from prophylactic to maximum clinically acceptable doses [46]. Although this could be a specific effect of dalteparin, these observations may also reflect the possibility that low-dose LMWH has different effects at lower and higher doses, similarly to the effects seen on trophoblast proliferation in vitro [32,35]. These findings are consistent with the observation from the Rodger et al meta-analysis that low-dose LMWH treatment was more effective at preventing pre-eclampsia than intermediate doses [18].…”

Section: Vascular Functionmentioning

confidence: 99%

Molecular actions of heparin and their implications in preventing pre‐eclampsia

Wat

Audette

Kingdom

2018

Journal of Thrombosis and Haemostasis

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Pre-eclampsia, a hypertensive disorder of pregnancy, continues to be a significant cause of global maternal morbidity. Low-dose aspirin remains the only standard-of-care prophylactic therapy for preventing pre-eclampsia, but is limited in efficacy. Heparin and its derivatives may further enhance the efficacy of aspirin therapy to prevent pre-eclampsia, but the mechanisms mediating this augmentative effect are not known. Although heparin is an anticoagulant agent, it also possesses many anticoagulant-independent properties that may be relevant in the prevention of pre-eclampsia, including effects on placental, vascular and inflammatory function. This review summarizes the non-anticoagulant properties of heparin, and extrapolates how these actions may influence the trajectory of pre-eclampsia pathogenesis as a means of pathway-specific therapy.

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Effects of low molecular weight heparin and heparin-binding epidermal growth factor on human trophoblast in first trimester

Cited by 23 publications

References 31 publications

Aspirin and Low-Molecular Weight Heparin Combination Therapy Effectively Prevents Recurrent Miscarriage in Hyperhomocysteinemic Women

Aspirin and Low-Molecular Weight Heparin Combination Therapy Effectively Prevents Recurrent Miscarriage in Hyperhomocysteinemic Women

Emerging nonanticoagulant role of low molecular weight heparins on extravillous trophoblast functions and on heparin binding–epidermal growth factor and cystein-rich angiogenic inducer 61 expression

Molecular actions of heparin and their implications in preventing pre‐eclampsia

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