Association between Placental Lesions, Cytokines and Angiogenic Factors in Pregnant Women with Preeclampsia

Weel, Ingrid C.; Baergen, Rebecca N.; Romao‐Veiga, Mariana; Borges, Vera Therezinha Medeiros; Ribeiro, Vanessa Rocha; Witkin, Steven S.; Bannwart-Castro, Camila F.; Peraçoli, José Carlos; Peraçoli, Maria Terezinha Serrão

doi:10.1371/journal.pone.0157584

Cited by 88 publications

(65 citation statements)

References 45 publications

(67 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In regard to the IL-10 expression levels, our results are in accordance with those of Makris et al [14] who, by immunohistochemistry and real-time RT-PCR, showed reduction in both protein and gene expressions of this anti-inflammatory cytokine in PE than those in the term control group. Correspondingly, Weel et al [12] observed the same difference with respect to IL-10 placental expression. To our knowledge, this is the first study to publish placental gene expression levels of IL1-RA in PE.…”

Section: Discussionmentioning

confidence: 70%

“…Benyo et al [11] used ELISA in placental homogenates and semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), and they observed that both protein and gene expressions of TNF-α were similar in the PE and term control group. In contrast, Weel et al [12], by ELISA in placental homogenates and immunohistochemistry, observed higher protein expression levels of TNF-α in PE than those in the term control group; however, they used homogenates that included both the fetal and maternal sides of the placenta. Our results about the placental gene expression of IL-6 also concur with Marusic et al [10] and Benyo et al [11].…”

Section: Discussionmentioning

confidence: 92%

See 1 more Smart Citation

Placental Proinflammatory State and Maternal Endothelial Dysfunction in Preeclampsia

Valencia

Zárate

Saucedo

et al. 2018

Gynecol Obstet Invest

View full text Add to dashboard Cite

Objective: To evaluate the placental and decidual gene expression and maternal and umbilical serum concentrations of tumor necrosis factor alpha, interleukin 6 (IL-6), IL-8, IL-10, IL-1 receptor antagonist (IL-1RA), intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 (VCAM-1), along with the proinflammatory/anti-inflammatory cytokine ratios in women with preeclampsia (PE) vs. women with normal pregnancy (NP), and to analyze PE classified as early- (EO) and late-onset (LO). Methods: This cross-sectional study was performed with 50 women with PE (EO n = 30, LO n = 20) and 50 women with NP. Tissue gene expression levels were measured by real-time RT-PCR. Cytokines and adhesion molecules serum concentrations were measured by immunoassays. Results: In PE, placental expression of IL-10 and IL-1RA was lower, while placental IL-8/IL-1RA ratio and maternal concentrations of VCAM-1 were higher vs. NP. In EO, placental expression of IL-10 was lower, while placental IL-8/IL-10 and IL-8/IL-1RA ratios were higher than LO and NP. Maternal concentrations of IL-6 were higher in LO than EO and NP. Throughout PE, maternal VCAM-1 concentrations were higher vs. NP. No significant differences were observed in the decidual expression and umbilical concentrations of the markers between the groups. Conclusion: PE associates with a proinflammatory placental state; however, EO associates with a proinflammatory placental state, while LO associates with systemic maternal inflammation. Both subtypes associated with maternal endothelial dysfunction.

show abstract

Section: Discussionmentioning

confidence: 70%

Section: Discussionmentioning

confidence: 92%

Placental Proinflammatory State and Maternal Endothelial Dysfunction in Preeclampsia

Valencia

Zárate

Saucedo

et al. 2018

Gynecol Obstet Invest

View full text Add to dashboard Cite

show abstract

“…NLRP3 inflammasome activation requires an already exaggerated inflammatory setting, as a priming signal is needed to achieve sufficient intracellular levels of NLRP3 and pro-IL-1b [15,54]. The choice of priming signal in the placenta was based on reports of elevated C5a and TNF-a in pre-eclampsia [28,32,[35][36][37][38][55][56][57], and supported by our discovery of C5a and TCC in the syncytium of pre-eclamptic placentas. The functional response confirms that C5a and TNF-a may serve as endogenous priming factors potentiating placental NLRP3 inflammasome activation.…”

Section: Discussionmentioning

confidence: 99%

Placental inflammation in pre-eclampsia by Nod-like receptor protein (NLRP)3 inflammasome activation in trophoblasts

Stødle

Silva

Tangerås

et al. 2018

Clinical and Experimental Immunology

View full text Add to dashboard Cite

Pre-eclampsia is associated with increased levels of cholesterol and uric acid and an inflamed placenta expressing danger-sensing pattern recognition receptors (PRRs). Crystalline cholesterol and uric acid activate the PRR Nod-like receptor protein (NLRP)3 inflammasome to release interleukin (IL)-1β and result in vigorous inflammation. We aimed to characterize crystal-induced NLRP3 activation in placental inflammation and examine its role in pre-eclampsia. We confirmed that serum total cholesterol and uric acid were elevated in pre-eclamptic compared to healthy pregnancies and correlated positively to high sensitivity C-reactive protein (hsCRP) and the pre-eclampsia marker soluble fms-like tyrosine kinase-1 (sFlt-1). The NLRP3 inflammasome pathway components (NLRP3, caspase-1, IL-1β) and priming factors [complement component 5a (C5a) and terminal complement complex (TCC)] were co-expressed by the syncytiotrophoblast layer which covers the placental surface and interacts with maternal blood. The expression of IL-1β and TCC was increased significantly and C5a-positive regions in the syncytiotrophoblast layer appeared more frequent in pre-eclamptic compared to normal pregnancies. In-vitro activation of placental explants and trophoblasts confirmed NLRP3 inflammasome pathway functionality by complement-primed crystal-induced release of IL-1β. This study confirms crystal-induced NLRP3 inflammasome activation located at the syncytiotrophoblast layer as a mechanism of placental inflammation and suggests contribution of enhanced NLRP3 activation to the harmful placental inflammation in pre-eclampsia.

show abstract

“…Although the emphasis on the toxic factors produced by an ischemic placenta has been on the balance between angiogenic and anti-angiogenic factors, evidence now suggests that cytokines, such as TNF-α and IL-10, are altered in early and late preeclampsia, and the changes correlate with the type of histopathological changes in the placenta(185). The importance of ischemic placental disease, not limited to preeclampsia, has been the subject of several recent studies, i.e., preterm labor, preterm PROM, fetal growth restriction, fetal death, and other complications of pregnancy(186–189).…”

Section: Mechanisms By Which Metformin May Prevent Preeclampsiamentioning

confidence: 99%

Metformin, the aspirin of the 21st century: its role in gestational diabetes mellitus, prevention of preeclampsia and cancer, and the promotion of longevity

Romero

Erez

Hüttemann

et al. 2017

American Journal of Obstetrics and Gynecology

194

120

View full text Add to dashboard Cite

Metformin is everywhere. Originally introduced in clinical practice as an anti-diabetic agent, its role as a therapeutic agent is expanding to include treatment of pre-diabetes, gestational diabetes, polycystic ovarian disease, and more recently, experimental studies, as well as observations in randomized clinical trials, suggest that metformin could have a place in the treatment or prevention of preeclampsia. This article provides a brief overview of the history of metformin in the treatment of diabetes, reviews the results of meta-analyses of metformin in gestational diabetes, and the treatment of obese non-diabetic pregnant women to prevent macrosomia. We highlight the results of a randomized clinical trial in which metformin administration in early pregnancy did not reduce the frequency of large-for-gestational-age infants (primary endpoint), but did decrease the frequency of preeclampsia (a secondary endpoint). The mechanisms by which metformin may prevent preeclampsia include a reduction in the production of anti-angiogenic factors (soluble vascular endothelial growth factor receptor-1 and soluble endoglin), and improving endothelial dysfunction, probably through an effect on the mitochondria. Another potential mechanism whereby metformin may play a role in the prevention of preeclampsia is its ability to modify cellular homeostasis and energy disposition, mediated by mTOR. Metformin has a molecular weight of 129 Dalton, and therefore, readily crosses the placenta. There is considerable evidence suggesting that this agent is safe during pregnancy. New literature on the role of metformin in the prevention of cancer, a chemotherapeutic adjuvant, and in prolonging life and protecting against aging, is briefly reviewed. Herein we discuss the mechanisms of action and potential benefits of metformin.

show abstract

Association between Placental Lesions, Cytokines and Angiogenic Factors in Pregnant Women with Preeclampsia

Cited by 88 publications

References 45 publications

Placental Proinflammatory State and Maternal Endothelial Dysfunction in Preeclampsia

Placental Proinflammatory State and Maternal Endothelial Dysfunction in Preeclampsia

Placental inflammation in pre-eclampsia by Nod-like receptor protein (NLRP)3 inflammasome activation in trophoblasts

Metformin, the aspirin of the 21st century: its role in gestational diabetes mellitus, prevention of preeclampsia and cancer, and the promotion of longevity

Contact Info

Product

Resources

About