TNFα concentrations and mRNA expression are increased in preeclamptic placentas

Wang, Yuping; Walsh, Scott W.

doi:10.1016/s0165-0378(96)00998-9

Cited by 182 publications

(116 citation statements)

References 26 publications

Supporting

Mentioning

106

Contrasting

Unclassified

Order By: Relevance

“…Other genes currently under investigation are likely to be involved in GH and PE predisposition such as those associated with blood pressure control (Morgan and Ward 1999), thrombophilia (Kupferminc et al 2000;Ozcan et al 2001) and oxidative stress (Broughton Pipkin and Roberts 2000;Wang and Walsh 1996), but results are contradictory, possibly due to differences in study design, genetic heterogeneity of the disorder, the genetic background of the populations studied, as well as genetic stratification and type I error (GOPEC Consortium 2005). The French-Canadian population is characterized by a founder effect (Heyer and Tremblay 1995).…”

Section: Discussionmentioning

confidence: 99%

The combination of ApoCIII, hepatic lipase and hormono sensitive lipase gene polymorphisms suggests an association with susceptibility to gestational hypertension

et al. 2007

View full text Add to dashboard Cite

Dyslipidemia and insulin resistance contribute to the endothelial cell dysfunction in hypertensive disorders of pregnancy (HDP) and increase the long-term risk of cardiovascular disease (CVD). The genes linking susceptibility to gestational hypertension (GH) and/or preeclampsia (PE) to the long-term risk of CVD are still unknown. We evaluated the potential association between 14 polymorphisms from six genes involved in lipid metabolism and insulin action and the risk of HDP: namely the lipoprotein lipase (LPL), hepatic lipase (LIPC), hormone sensitive lipase (LIPE), cholesteryl ester transfer protein (CETP), ApoCIII and ApoE gene polymorphisms. Overall, 169 women with HDP [proteinuria (PE) and gestational hypertension without proteinuria (GH)] and 169 controls matched for age and year of delivery were genotyped. Homozygosity of the -514T allele of the -514C > T polymorphism (LIPC gene) decreased the risk of GH (OR = 0.17, CI 95 : 0.02-0.76), while there were more -60G carriers of the -60C > G LIPE gene polymorphism (OR = 3.51, CI 95 :1.02-12.10) among GH cases, but not in PE cases. The common ApoCIII two-locus -482CC/3238CC genotype was lower in women with GH compared with controls (OR = 0.53, CI 95 : 0.3-0.9). The combined frequency of at-risk genotypes was higher in cases of GH compared with controls [one at-risk genotype: OR = 3.38 (95% CI: 0.48-41.8); two or more at-risk genotypes: OR = 7.14 (95% CI: 1.21-92.3, P = 0.01)], suggesting a gene-dose effect. We conclude that the combined effect of LIPC, LIPE and ApoCIII gene polymorphisms may increase the likelihood of GH, but seemingly not of PE.

show abstract

Section: Discussionmentioning

confidence: 99%

The combination of ApoCIII, hepatic lipase and hormono sensitive lipase gene polymorphisms suggests an association with susceptibility to gestational hypertension

et al. 2007

View full text Add to dashboard Cite

show abstract

“…27 There is also a report of increased TNF-␣ production by preeclamptic placentas. 28 If hypoxia is a stimulus, then it is perhaps not surprising that invasive cytotrophoblast, with oxygenation determined by nonanastamosing basal arteries and diffusion through several cell layers of decidua, would be affected whereas villous cytotrophoblast exposed to extensively comingled intervillous blood flow would not. Our findings of changes in the basal plate/placental bed suggest that oxidative stress is more pronounced at sites where maternal and fetal tissues intermingle, as distinct from changes in purely fetal tissue (the villous placenta).…”

Section: Discussionmentioning

confidence: 99%

Invasive Cytotrophoblasts Manifest Evidence of Oxidative Stress in Preeclampsia

Many

Hubel

Fisher

et al. 2000

The American Journal of Pathology

250

150

View full text Add to dashboard Cite

In preeclampsia, poor placental perfusion may result in maternal endothelial dysfunction, but the pathways involved are largely unknown. Candidate placental mediators include products of oxidative stress released into the maternal circulation. Xanthine oxidase has been implicated in postischemic-reperfusion injury via the generation of superoxide anion radicals (superoxide; O 2 .؊ ) and hydrogen peroxide. We examined placentas and placental bed curettings and/or biopsies from preeclamptic control pregnant women to test the hypothesis that xanthine oxidase is a mediator of oxidative stress in placentas from women with preeclampsia. The expression of xanthine dehydrogenase/xanthine oxidase holoenzyme and the activity of xanthine oxidase, the isoform known to generate reactive oxygen species, were increased in a subpopulation of cytotrophoblasts of preeclamptic women. Additionally, the expression of superoxide dismutase, which would scavenge superoxide produced by xanthine oxidase, was reduced in the same cells. Preeclampsia, a pregnancy-specific disorder, is the leading cause of maternal mortality in the Western world and increases perinatal mortality fivefold. The clinical diagnosis is based on the new onset of hypertension and the appearance of proteinuria and edema during pregnancy. It is evident, however, that these findings are a small component of a multisystemic disease that reduces perfusion to virtually all of the organs in the body. 1 The hypothesis has been advanced that much of the disease could be explained by alterations in the function of vascular endothelium. Increasing data support this hypothesis. 2 The more complete hypothesis posits that the placenta, likely in response to reduced perfusion, produces a circulating factor(s) that alters endothelial cell function. 2 Among the candidate molecules are products resulting from oxidative stress. 3 Oxidative stress, the result of freeradical generation in excess of protective mechanisms, is suggested as an important component of other disorders that affect endothelial function, including diabetes and atherosclerosis. 4,5 Evidence for oxidative stress in preeclampsia includes elevated lipid hydroperoxides or their metabolites and reduced plasma antioxidant activity. 3,6 -8 Xanthine oxidase, which metabolizes xanthine and hypoxanthine to uric acid with production of superoxide and hydrogen peroxide, is an integral mediator of reactive oxygen species generation in many settings. Usually, this enzyme is present as the holoenzyme xanthine dehydrogenase/xanthine oxidase (XDH/XO). The dehydrogenase isoform (XDH) converts purines to uric acid with reducton of nicotinamide-adenine dinucleotide (NAD) to reduced NAD (NADH). With hypoxia and in response to several cytokines, XDH/XO synthesis increases, and the conversion of the enzyme to the XO form is enhanced. 9 Reduced organ perfusion and subsequent reperfusion are proposed to result in increased XO during reduced flow and in subsequent formation of reactive oxygen species with reperfusion. The inadequate pla...

show abstract

“…50,68,69 Freeman and colleagues recently examined changes in inflammatory markers prospectively during pregnancy and the current inflammatory status of women who had a pregnancy complicated by preeclampsia 20 years previously against matched controls and found that preeclampsia was associated with short-and long-term changes in inflammatory status. 69 Whereas Armanini and Calo 70 suggested that aldosterone could play an important role in the genesis of this increased susceptibility of inflammatory process in preeclampsia, other factors such as obesity, diabetes, and placental ischemia could also be involved.…”

Section: Cytokinesmentioning

confidence: 99%