The Endothelin System: A Critical Player in the Pathophysiology of Preeclampsia

Granger, Joey P.; Spradley, Frank T.; Bakrania, Bhavisha

doi:10.1007/s11906-018-0828-4

Cited by 65 publications

(44 citation statements)

References 69 publications

(75 reference statements)

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“…The early identification of PE can assist obstetricians in assuming pivotal measures for timely intervening for the avoidance or reduction of the occurrence of adverse pregnancy outcomes. A number of studies were conducted about the pathogenesis of PE . Among these etiological theories, the reduced migration and invasion abilities of trophoblasts are the broadly accepted causes.…”

Section: Discussionmentioning

confidence: 99%

miR‐215‐5p decreases migration and invasion of trophoblast cells through regulating CDC6 in preeclampsia

Yang

Meng

2020

Cell Biochemistry & Function

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Preeclampsia (PE) is a serious disease that occurs after 20 weeks during pregnancy.There are some aberrant microRNAs (miRNAs) that are associated with the etiology of PE. As discovered by scholars, there was an increased level of miR-215-5p in plasma of PE patients compared with the control group; nonetheless, there is still no knowledge of the mechanism of miR-215-5p in PE. We carried out the comparison of the expression levels of miR-215-5p, and the supposed target gene cell division cycle 6 (CDC6) in 30 placentas from PE patients as well as 30 placentas from normal pregnant women. The verification of the impacts of miR-215-5p and CDC6 was carried out by functional assays in HTR-8/SVneo cells transfected with the miR-215-5p mimic or siR-CDC6. As indicated by findings, miR-215-5p showed an apparent increase; conversely, CDC6 was inhibited in the experiment group. The upregulation of miR-215-5p inhibited both the migration and invasive potential of trophoblasts, besides decreasing the G1-S transition and downregulating CDC6 in HTR-8/SVneo cells; nonetheless, it did not significantly impact the cell proliferation. Furthermore, siR-CDC6 replicated the functions of the miR-215-5p mimic. Also, the miR-215-5p mimic and siR-CDC6 both decreased the epithelial-mesenchymal transition (EMT) with additional E-cadherin level and decreased the expressions of N-cadherin as well as vimentin in trophoblast cells. To conclude, miR-215-5p decreased not only the migration but also the invasion of trophoblasts through regulating CDC6, which indicated that miR-215-5p might be associated with the etiology of PE.Significance of the study: More and more attention has been paid on the roles of miRNAs in the pathogenesis of PE. However, there is no study of miR-215-5p in the etiology of PE. We first investigated the mechanism of miR-215-5p in placental tissues and HTR-8/SVneo cells. It was suggested that miR-215-5p decreased the abilities of migration and invasion of trophoblasts through regulating CDC6 in PE. miR-215-5p might be used as an target for the early diagnosis and treatment of PE in the future. K E Y W O R D S preeclampsia, miR-215-5p, CDC6, EMT, placenta Abbreviations: CCK-8, Cell Counting Kit-8; CDC6, cell division cycle 6; cDNA, complementary DNA; DMEM, Dulbecco's modified Eagle's medium; EMT, epithelial-mesenchymal transition.; FBS, fetal bovine serum; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; miRNA, microRNA; PBS, phosphate-buffered saline solution; PE, preeclampsia; PI, propidium iodide; PVDF, polyvinylidene fluoride; SDS-PAGE, sodium dodecyl sulfate polyacrylamide gel electrophoresis.

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Section: Discussionmentioning

confidence: 99%

miR‐215‐5p decreases migration and invasion of trophoblast cells through regulating CDC6 in preeclampsia

Yang

Meng

2020

Cell Biochemistry & Function

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“…Preeklampsi hastalarının dolaşımındaki artmış ET-1 seviyelerinin hastalığın şiddeti ile uyumlu olduğunu gösteren çalışmalar mevcuttur. Ayrıca preeklampsi hastalarında belirlenmiş yüksek matriks metalloproteinaz aktivasyonunun ET-1 düzeyinin ve duyarlılığının artışına ve vazokonstrüksiyon lehine dengelerin bozulmasına yol açtığı bilinmektedir (50) . • Preeklampli gebelerin serumlarının in vitro ortamda insan umbilikal ven endotel hücre kültüründe aktivasyona yol açması (51)(52)(53)(54)(55) .…”

Section: Preeklampsi̇ Ve Endotel Di̇sfonksi̇yonuunclassified

Molecular Mechanisms of Endothelial Function and Dysfunction in Human Diseases

Günel¹,

Çelik²,

Küçükkaya³

et al. 2020

IKSST

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Vasküler endotel, kan damarlarının tüm iç yüzeylerini örten birçok önemli fizyolojik ve patolojik reaksiyonu düzenleyen önemli bir organdır. Bir bariyer olarak endotel, moleküllerin transferini düzenler ve yarı geçirgen bir tabaka gibi davranır. Yaralanmalara veya patolojik koşullara yanıt olarak yeni damar oluşumunu (anjiyogenez) hızla başlatma kapasitesini de korurlar. Anjiyogenez, dokulara oksijen ve besin sağlamak amacıyla var olan damarlardan yeni damarlar oluşum sürecidir. Kan damarları ve bileşenleri, hemostaz, tromboz ve inflamasyon için kritik öneme sahiptir. Anjiyogenez oldukça sıkı bir şekilde regüle edilen çok sayıda farklı hücre tiplerinin olaya karıştığı kompleks bir süreçtir. Oldukça karmaşık şekilde düzenlenen bu süreçte yer alan çok sayıda mediyatör vardır. Bu mediyatörler; vazodilatasyonu sağlayan nitrik oksit (NO: endotel kaynaklı gevşetici faktör) ve prostasiklin (PGI2) ile vazokonstrüksiyonu sağlayan endotelin-1 (ET-1), platalet aktivasyon faktörü (PAF) ve Anjyotensin II'dir. Endotel disfonksiyonu (ED), endotel tarafından sağlanan vazodilatasyon ve vazokonstrüksiyon arasındaki dengesizlikten dolayı ortaya çıkan patolojik durumdur. Endoteldeki düzensizlikler organizma için olumsuz sonuçlar doğuracak patolojik işlevlere dönüşür. Endotel disfonksiyonu, hipertansiyon, koroner arter hastalığı, kronik kalp yetmezliği, periferik arter hastalığı, diyabet, kanser ve preeklampsi gibi çeşitli hastalıkların patogenezinde rol oynarlar. Normal ve disfonksiyona uğramış endotel arasındaki farklılıklar, gelişmiş antianjiyogenez için yeni terapötik olanaklar sunabilir. Bu derleme, endotel hücrelerinin, mediyatörlerin ve sinyal yolaklarının önemli hastalıkların her aşamasında gerçekleştirdiği işlevleri ve tedavi ipuçlarını anlatmak için yazılmıştır.

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“…The cause of pre‐eclampsia remains unclear. Relevant studies have shown that it is closely related to a reduction in the conversion of maternal spiral artery, 12 placental hypoperfusion 13 and systemic inflammation 14 during early pregnancy. Angiogenesis is the basis of normal placental development.…”

Section: Introductionmentioning

confidence: 99%

Levels of serum Hoxb3 and sFlt‐1 in pre‐eclamptic patients and their effects on pregnancy outcomes

Zhou

Guo

Sun

et al. 2020

J of Obstet and Gynaecol

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Aim: We aimed to explore a new approach and theoretical basis for the diagnosis, treatment and prognosis of pre-eclampsia. Methods: In total, 103 pre-eclamptic patients (study group: SG) and 100 healthy pregnant women (control group: CG) were enrolled. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression level of serum Hoxb3. Enzyme-linked immunosorbent assay was used to detect the content of serum sFlt-1. Pregnancy outcomes in the two groups were recorded, and the correlations of the levels of Hoxb3 and sFlt-1 with the pregnancy outcomes were analyzed. Results: The relative expression of serum Hoxb3 mRNA in the CG was significantly higher than that in the SG, whereas the content of serum sFlt-1 in the CG was significantly lower than that in the SG. Compared with the CG, the SG had a significantly lower number of spontaneous deliveries, higher number of cesarean deliveries and significantly higher number of uneventful perinatal births. The incidences of intrauterine growth restriction, intrauterine distress, premature infants and neonatal deaths in perinatal infants in the SG were significantly higher than those in the CG. According to the analysis of receiver operating characteristic curves, the areas under the curves of Hoxb3, sFlt-1 and their combined detection for diagnosing preeclampsia were 0.799, 0.856 and 0.930, respectively. The areas under the curves for predicting poor perinatal outcomes were 0.724, 0.828 and 0.871, respectively. Conclusion: In conclusion, Hoxb3 and sFlt-1 have certain reference significance for the risk evaluation of pre-eclampsia and the adverse pregnancy outcomes of pre-eclampsia women.

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The Endothelin System: A Critical Player in the Pathophysiology of Preeclampsia

Cited by 65 publications

References 69 publications

miR‐215‐5p decreases migration and invasion of trophoblast cells through regulating CDC6 in preeclampsia

miR‐215‐5p decreases migration and invasion of trophoblast cells through regulating CDC6 in preeclampsia

Molecular Mechanisms of Endothelial Function and Dysfunction in Human Diseases

Levels of serum Hoxb3 and sFlt‐1 in pre‐eclamptic patients and their effects on pregnancy outcomes

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