Low molecular weight heparin stimulates myometrial contractility and cervical remodeling in vitro

Ekman-Ordeberg, Gunvor; Hellgren, Margareta; Åkerud, Anna; Andersson, Eva; Dubicke, Aurelija; Sennström, Maria; Byström, Birgitta; Tzortzatos, Gerasimos; Gomez, Maria F.; Edlund, Måns; Lindahl, Ulf; Malmström, Anders

doi:10.1080/00016340903176818

Cited by 27 publications

(39 citation statements)

References 22 publications

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“…Our findings may imply a role of LMWH on duration and initiation of labour Similar as those reported by Ekman and coworkers [10]. They also report in a laboratory setting that LMWH stimulates myometrial contractility and cervical remodeling in vitro [14]. This theory would also give an explanation to the increased risk of prematurity.…”

Section: Discussionsupporting

confidence: 90%

The effect of low molecular weight heparin (dalteparin) on duration and initiation of labour

Isma

Svensson

Lindblad

et al. 2009

J Thromb Thrombolysis

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It has recently been reported that women treated with low molecular weight heparin (LMWH) during pregnancy had 3 h shorter duration of delivery. The aim of the present study was to evaluate whether LMWH (dalteparin) affects labour. From January 1996 to December 2005, 217 consecutive pregnancies, out of 34 216 newborn (prevalence 0.6%) that were given thromboprophylaxis with dalteparin (usually 5,000 IU once daily). These 217 consecutive pregnancies were compared to an unselected control group (n = 1,499) of gravidae. Main outcome was time in first and second stage of labour and gestational age at delivery. Among nulliparous women, there were significantly fewer women with prolonged first stage of labour as compared to controls (4.1% vs. 8.5%, P = 0.047). In addition, the duration of first stage of labour was 1 h shorter among those treated with LMWH (5.2 vs. 6.2 h, P = 0.06). There were no such differences among parous women. The risk of prematurity, profuse blood loss, and postpartum anaemia was almost doubled among those treated with LMWH (11.5% vs. 5.9%, P = 0.002, 10.6% vs. 5.9%, P < 0.001, and 12.9% vs. 8.7%, P = 0.048, respectively). Treatment with a prophylactic dose of LMWH (dalteparin) during pregnancy was related to fewer women with prolonged first stage of labour, but also to an increased risk of prematurity and blood loss complications.

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Section: Discussionsupporting

confidence: 90%

The effect of low molecular weight heparin (dalteparin) on duration and initiation of labour

Isma

Svensson

Lindblad

et al. 2009

J Thromb Thrombolysis

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“…The mechanisms of the activator effect of heparin on the LN capsular SM cells are not quite clear. The stimulatory effect of heparin on SM contractility was previously observed on other objects [6] and could be due to changes in the physicochemical characteristics of the perimembrane layer. Modifi cation of interactions between glycoproteins of the plasma and lymph and calcium channels in the plasmalemma under the effect of heparin has been demonstrated [9].…”

Section: Resultssupporting

confidence: 55%

Effect of Heparin on Contractile Activity of Lymph Node Capsule

Pan’kova

Lobov

2015

Bull Exp Biol Med

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Experiments on smooth muscle strips isolated from the capsule of bovine mesenteric lymph node showed that heparin low concentrations (0.010-0.025 U/ml) stimulating spontaneous isometric phasic contractions of smooth muscles, but higher heparin concentrations reduced or even completely eliminated these contractions. The inhibitory effects of heparin were presumably realized via stimulation of NO production by endothelial cells of the subcapsular space followed by activation of ATP-sensitive potassium channels of capsular myocytes and via modulation of prostaglandin synthesis.

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“…Ekman-Ordeberg and colleagues. [67] have demonstrated that low molecular weight heparin increased IL-8 secretion in cervical fibroblasts. This area of research has great potential for targeting the mechanisms involved in cervical change during pregnancy.…”

Section: Importance Of the Studymentioning

confidence: 96%

The transcriptome of cervical ripening in human pregnancy before the onset of labor at term: Identification of novel molecular functions involved in this process

Hassan¹,

Romero²,

Tarca³

et al. 2009

The Journal of Maternal-Fetal & Neonatal Medicine

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Objective. The aim of this study was to identify changes in the cervical transcriptome in the human uterine cervix as a function of ripening before the onset of labor. Study Design. Human cervical tissue was obtained from women at term not in labor with ripe (n ¼ 11) and unripe (n ¼ 11) cervices and profiled using Affymetrix GeneChip 1 HGU133Plus2.0 arrays. Gene expression was analyzed using a moderated t-test (False Discovery Rate 5%). Gene ontology and pathway analysis were performed. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used for confirmation of selected differentially expressed genes. Results.(1) Ninety-one genes were differentially expressed between ripe and unripe groups. (2) Cervical ripening was associated with enrichment of specific biological processes (e.g. cell adhesion, regulation of anatomical structure), pathways and 11 molecular functions (e.g. extracelluar matrix (ECM)-structural constituent, protein binding, glycosaminoglycan binding). (3) qRT-PCR confirmed that 9 of 11 tested differentially expressed genes (determined by microarray) were upregulated in a ripe cervix (e.g. MYOCD, VCAN, THBS1, COL5A1). (4) Twenty-three additional genes related to ECM metabolism and adhesion molecules were differentially regulated (by qRT-PCR) in ripe cervices. Conclusion.(1) This is the first description of the changes in the human cervical transcriptome with ripening before the onset of labor. (2) Biological processes, pathways and molecular functions were identified with the use of this unbiased approach. (3) In contrast to cervical dilation after term labor, inflammation-related genes did not emerge as differentially regulated with cervical ripening. (4) Myocardin was identified as a novel gene upregulated in human cervical ripening.

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Low molecular weight heparin stimulates myometrial contractility and cervical remodeling in vitro

Cited by 27 publications

References 22 publications

The effect of low molecular weight heparin (dalteparin) on duration and initiation of labour

The effect of low molecular weight heparin (dalteparin) on duration and initiation of labour

Effect of Heparin on Contractile Activity of Lymph Node Capsule

The transcriptome of cervical ripening in human pregnancy before the onset of labor at term: Identification of novel molecular functions involved in this process

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