The function of elevated plasma fibronectin in preeclampsia

Brubaker, Daniel B.; Ross, Michael G.; Marinoff, David N.

doi:10.1016/0002-9378(92)91663-u

Cited by 55 publications

(26 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The analysis of the available data points to the central role of TNF-α as a mediator participating in vascular endothelial damage and as a strong modulator in the release of vasoactive substances such as endothelin, VCAM-1 and ICAM-1. This expression may increase leukocyte-endothelial cell interactions and, in addition, may increase microvascular permeability [61] and serum levels of fibronectin (due to vascular injury) as a marker of organ involvement in preeclamptic women [42,62,63]. The resulting outcome is variable clinical phenotypes, e.g.…”

Section: Discussionmentioning

confidence: 99%

TNF-α G308A Gene Polymorphism Has an Impact on Renal Function, Microvascular Permeability, Organ Involvement and Severity of Preeclampsia

Žúbor

Dokus²,

Zigo³

et al. 2014

Gynecol Obstet Invest

View full text Add to dashboard Cite

Background/Aims: Preeclampsia (PE) is a life-threatening complication of pregnancy that is associated with a high rate of maternal and perinatal morbidity and/or mortality worldwide. If untreated, it can progress to eclampsia, which can result in the death of the mother, the fetus or both. The etiology of PE is still uncertain; however, recently the role of the immune system has gained in importance. The role of tumor necrosis factor-α (TNF-α), a cytokine involved in inflammation processes, has been widely investigated in obstetric disorders. The aims of the present study were to investigate the effect of TNF-α gene G308A (rs1800629) polymorphism on disease risk, renal function, microvascular permeability, endothelial cell dysfunction and organ involvement in women with PE. Methods: Initially, 102 3rd-trimester pregnant women (preeclamptic cases and healthy controls) with singleton pregnancy were invited for participation, of which 76 were genotyped for TNF-α G308A polymorphism and evaluated for plasma levels of soluble vascular cell adhesion molecule-1 (sVCAM-1), fibronectin and TNF-α, which were tested for correlations with the profile of PE. The odds ratio (OR) and 95% confidence intervals obtained from unconditional logistic regression were used to test the association between the TNF-α polymorphism and PE risk. For continuous variables, we applied Student's t test and, for categorical variables, the Pearson χ² or Fisher's exact test. The two-way ANOVA test with Bonferroni correction was used in multivariate analyses. Results: The A allele was more frequent in cases than controls (22.4 vs. 13.2%), which increased disease risk (OR = 2.73). Maternal serum levels of TNF-α, sVCAM-1 and fibronectin were significantly increased in cases (855.8 ± 385.1 pg/ml, 1,243 ± 671 ng/ml, 0.308 ± 0.231 g/l, respectively) compared to controls (301.1 ± 156.1 pg/ml, 651 ± 250 ng/ml, 0.218 ± 0.101 g/l, respectively; p < 0.0001, p < 0.0001 and p = 0.031, respectively), and these levels showed an increasing trend with the mutant allele genotype. Moderate and severe proteinuria was higher in rs1800629 allele A subjects compared to G/G carriers (53.8 vs. 14.3% (p < 0.05) and 13.0 vs. 4.7% (p < 0.01), respectively). The adverse effect of rs1800629 allele A on renal function was confirmed by increased plasma creatine levels, urinary protein excretion and lower tubular resorption rate in preeclamptic patients. Moreover, rs1800629 allele A preeclamptic carriers showed higher serum levels of fibronectin and sVCAM-1 compared to G/G homozygotes. Conclusion: This study reveals a possible association between clinical and laboratory manifestations of PE and the TNF-α gene G308A (rs1800629) polymorphism.

show abstract

Section: Discussionmentioning

confidence: 99%

TNF-α G308A Gene Polymorphism Has an Impact on Renal Function, Microvascular Permeability, Organ Involvement and Severity of Preeclampsia

Žúbor

Dokus²,

Zigo³

et al. 2014

Gynecol Obstet Invest

View full text Add to dashboard Cite

show abstract

“…Deranged endothelial cell function is indicated by the presence of endotheliosis, a prominent vascular lesion in those severely affected, which regresses after delivery (Roberts et al 1989). Elevated blood fibronectin (Brubaker et al 1992) and factor VIII antigen levels (Roberts et al 1989) are additional markers of endothelial cell damage. Dysfunction of the endothelium is also manifested by increased permeability of capillaries to fluid and proteins, as assessed by more rapid disappearance of protein bound Evans Blue from the maternal circulation (Roberts et al 1989).…”

Section: Changes In Pre-eclampsia a N D Fetal Growth Retardationmentioning

confidence: 99%

Autacoids and Control of Human Placental Blood Flow

Boura

Walters

Read

et al. 1994

Clin Exp Pharma Physio

View full text Add to dashboard Cite

SUMMARY1. Humans have a haemochorial, villous placenta. Uterine blood passes through maternal sinuses, bathing placental villi through which fetal blood circulates. Blood flow through each circulation is high and vascular resistance low. This haemodynamic situation is essential for efficient placental function.2. The low placental vascular resistance is due to a lack of nervous influences together with pregnancy-induced changes promoting vasodilatation. Increases occur in output of the vasodilators prostacyclin and nitric oxide and also in membrane sodium pump activity.3. Many autacoids are present in umbilical blood. Fetal vessels of the placenta develop intense vasoconstriction in the presence of some autacoids, such as thromboxane A2 and prostaglandins Fza and E2, and respond weakly to others, such as angiotensin I1 and 5-hydroxytryptamine. Nevertheless, vasodilator influences predominate.4. The diseases of pre-eclampsia and fetal growth retardation are associated with reduced output of nitric oxide and prostacyclin and with increased production of thromboxane A2 and endothelin-1 . These changes promote vasoconstriction, increased vascular sensitivity to vasoconstrictor stimuli, platelet aggregation and intravascular coagulation, retarding blood flow and fetoplacental growth.5. Aspirin and glyceryl trinitrate have been investigated for possible therapeutic use in preeclampsia and fetal growth retardation. Improved drug therapy is likely as knowledge increases of the importance of autacoids in normal placental function and in the changes that occur during disease.

show abstract

“…In women with established preeclampsia total plasma fibronectin levels are elevated [5,6] and exhibit the most pronounced changes when compared to other markers of endothelial injury, clotting and fibrinolysis. There is an inverse correlation between high levels of fibronectin and low levels of antithrombin III [7] suggesting a hypercoagulable condition with fibrin deposition.…”

Section: Introductionmentioning

confidence: 98%

“…Less than 5% of the total pool of plasma fibronectin consists of an isoform, ED1 + cellular fibronectin, with an extra type-III domain. This fibronectin splice variant is mainly localised to the endothelium and thereby considered to be more representative of endothelial injury [6,9,10]. In preeclampsia there probably is a direct release of fibronectin into the plasma from damaged endothelium, although an increased synthesis may also contribute.…”

Section: Introductionmentioning

confidence: 99%

Total Fibronectin in Maternal Plasma as a Predictor for Preeclampsia

Gredmark¹,

Bergman²,

Hellström

1999

Gynecol Obstet Invest

View full text Add to dashboard Cite

Objective: To assess the ability of measuring total maternal plasma fibronectin in predicting the risk of developing preeclampsia. Method: In a cohort of 657 initially normotensive pregnant nulliparous women blood samples were collected at 26, 30 and 34 weeks of gestation. After delivery 3 groups were selected for measurement of total plasma fibronectin. The first group comprised 24 women who developed preeclampsia; the second 21 women who developed gestational hypertension, and the third 89 age-matched controls who remained normotensive. Results: In women who developed preeclampsia the fibronectin levels were higher at 26 (p < 0.01), 30 (p < 0.001) and 34 weeks of gestation (p < 0.001) than in pregnant controls. In the general population of pregnant nulliparous women the estimated risk of subsequent preeclampsia correlated with the fibronectin level at each measurement. In women with fibronectin levels within the 25th percentile at the 26th week of gestation, the risk was ≤1.9% and within the 90th percentile ≥6.2%. The change in fibronectin levels between 26 and 34 weeks of gestation was the only variable that remained statistically associated with preeclampsia (p = 0.0002) in multivariate analysis. In this model the risk figures for the corresponding percentiles were ≤1.0 and ≥5.8%, respectively. Conclusion: Longitudinal assessment of the change in total fibronectin levels predicted preeclampsia slightly better than cross-sectional analysis of fibronectin at any gestational age. Nevertheless, measurement of total fibronectin in maternal plasma could not be proven to be a useful clinical predictor for preeclampsia in a general obstetric population of nulliparous women.

show abstract

The function of elevated plasma fibronectin in preeclampsia

Cited by 55 publications

References 24 publications

TNF-α G308A Gene Polymorphism Has an Impact on Renal Function, Microvascular Permeability, Organ Involvement and Severity of Preeclampsia

TNF-α G308A Gene Polymorphism Has an Impact on Renal Function, Microvascular Permeability, Organ Involvement and Severity of Preeclampsia

Autacoids and Control of Human Placental Blood Flow

Total Fibronectin in Maternal Plasma as a Predictor for Preeclampsia

Contact Info

Product

Resources

About