Down-regulation of soluble fms-like tyrosine kinase 1 expression in invasive placentation

Shainker, Scott A.; Dannheim, Katelyn; Gerson, Kristin D.; Neo, Dayna; Zsengellér, Zsuzsanna K.; Pernicone, Elizabeth; Karumanchi, S. Ananth; Hacker, Michele R.; Hecht, Jonathan L.

doi:10.1007/s00404-017-4432-7

Cited by 23 publications

(10 citation statements)

References 21 publications

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“…In GDM-PE, sFlt1 down-regulation could exacerbate the mild hypervascularization induced by PlGF overexpression on placental vasculature. Our data are consistent with Shainker et al that reported lower sFlt1 expression in hyperperfused placentae, suggesting a functional role for sFlt1 in invasive placental implantation 54 . Differently by PE, where high sFlt1 expression is associated with shallow placentation and placental hypoperfusion 55,56 , placental sFlt1 downregulation in GDM-PE could result in invasive placentation and deeper implantation along with hyperperfusion as previously suggested by McMahnon et al 57 .…”

Section: Discussionsupporting

confidence: 93%

Placental and maternal sFlt1/PlGF expression in gestational diabetes mellitus

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Giuffrida

Moretti

et al. 2021

Sci Rep

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Gestational diabetes mellitus (GDM) and preeclampsia (PE) are both characterized by endothelial dysfunction and GDM women have higher incidence of PE. The placenta plays a key role in PE pathogenesis but its contribution to PE during GDM remains unclear. Herein, we compared placental and maternal blood anti-angiogenic soluble fms-like tyrosine kinase-1 (sFlt1) and pro-angiogenic Placental Growth Factor (PlGF) expressions in GDM and GDM-PE pregnancies compared to controls (CTRL) and PE cases. Electrochemiluminescence immunoassays showed a significantly higher maternal blood sFlt1/PlGF values in GDM-PE relative to CTRL and GDM pregnancies. We reported that placental PlGF gene expression was significantly decreased in GDM, PE and GDM-PE relative to CTRL. However, PlGF protein levels were significantly increased in GDM and GDM-PE relative to CTRL and PE placentae. Finally, sFlt1 gene expression was significantly increased in PE relative to CTRL, GDM and GDM-PE placentae. In contrast, sFlt1 protein expression was significantly decreased in GDM-PE relative to CTRL, GDM and PE placentae. Finally, higher sFlt1/PlGF ratio in GDM-PE maternal blood suggest that sFlt1 overproduction is related to PE onset also in GDM pregnancies even though characterized by a less severe endothelial dysfunction in terms of angiogenic biomarkers.

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Section: Discussionsupporting

confidence: 93%

Placental and maternal sFlt1/PlGF expression in gestational diabetes mellitus

Nuzzo

Giuffrida

Moretti

et al. 2021

Sci Rep

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“…Severe, early-onset preeclampsia is associated with inefficient physiological placental invasion and hypoperfusion, leading to increased sFlt-1 expression and ultimately the clinical phenotype of proteinuria and hypertension [ 20 , 21 ]. In contrast, invasive placentation results in deep implantation and hyperperfusion, along with suppressed local sFlt-1 expression [ 22 ] as demonstrated by decreased expression of sFlt-1 in villous trophoblasts in PAS patients, specifically placenta increta and percreta [ 23 ].…”

Section: Molecular Biologymentioning

confidence: 99%

Placenta Accreta Spectrum: A Review of Pathology, Molecular Biology, and Biomarkers

et al. 2018

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Background. Placenta accreta spectrum (PAS) is a condition of abnormal placental invasion encompassing placenta accreta, increta, and percreta and is a major cause of severe maternal morbidity and mortality. The diagnosis of a PAS is made on the basis of histopathologic examination and characterised by an absence of decidua and chorionic villi are seen to directly adjacent to myometrial fibres. The underlying molecular biology of PAS is a complex process that requires further research; for ease, we have divided these processes into angiogenesis, proliferation, and inflammation/invasion. A number of diagnostic serum biomarkers have been investigated in PAS, including human chorionic gonadotropin (HCG), pregnancy-associated plasma protein-A (PAPP-A), and alpha-fetoprotein (AFP). They have shown variable reliability and variability of measurement depending on gestational age at sampling. At present, a sensitive serum biomarker for invasive placentation remains elusive. In summary, there are a limited number of studies that have contributed to our understanding of the molecular biology of PAS, and additional biomarkers are needed to aid diagnosis and disease stratification.

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“…Whereas in the placenta from the accreta spectrum cases, the invasive placenta did not show a significant difference in sFlt-1 expression. 24 Ostaz et al reported that there was a decrease in oxidative stress in placenta accreta, and an invasion of the raised placenta and a high oxidative stress in preeclamsia. However, on the placenta accreta spectrum, there was a decrease in the level of oxidative stress, which is probably related to a decrease in the concentration of antio-angiogenic factor, sFlt-1.…”

Section: Discussionmentioning

confidence: 99%

Soluble FMS-Like Tyrosine Kinase: Role in placenta accreta spectrum disorder

et al. 2021

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Background: Placenta accreta is a pregnancy condition where the placenta's blood vessels attach too deeply to the uterine wall. Incidence of placenta accreta is increasingly seen today as the rate of cesarean section increases, however, the exact pathophysiology of this condition is still not fully understood. Soluble fms-like tyrosine kinase-1 (sflt-1) as a protein produced by the placenta was found to be decreased in placenta accreta, Therefore we aim to see if sflt-1 has a role in the development of placenta accreta. Methods: This study involved 40 samples from patients that had been diagnosed with placenta accreta spectrum disorder (case group), and 40 samples from patients with normal pregnancies (control group) at Rumah Skit Umum Pusat H.Adam Malik (RSUP) Haji Adam Malik Medan, in Indonesia. Diagnosis of placenta accreta syndrome was based on Placenta Accreta Spectrum Score (PAS), and International Federation of Gynecology and Obstetrics (FIGO) classification of placenta accreta spectrum disorder.Analyses were performed by independent t-test, man Whitney U test, and Kruskal-Wallis analysis test, with a P-value <0.05 considered as statistically significant (95%CI). Results: Based on this study, we found that the sFlt-1 level in the case group was lower than the control group. Data analysis using the Kruskal-Wallis test showed that there was a difference in sFlt-1 levels in this study group (p = 0.02), which was further evaluated with post hoc analysis using Mann. Whitney U test. The results indicated that there were significant differences between the control and PAS 0, PAS1, and PAS 2 (p = 0.043; p = 0.002; p = 0.03). Conclusion: sFlt-1 levels decreased in placental invasive pregnancies compared to normal pregnancies, however, this still needs to be investigated further in a multi-center study, considering that sFlt-1 levels are also influenced by ethnicity and other conditions that cannot be excluded in this study.

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Down-regulation of soluble fms-like tyrosine kinase 1 expression in invasive placentation

Cited by 23 publications

References 21 publications

Placental and maternal sFlt1/PlGF expression in gestational diabetes mellitus

Placental and maternal sFlt1/PlGF expression in gestational diabetes mellitus

Placenta Accreta Spectrum: A Review of Pathology, Molecular Biology, and Biomarkers

Soluble FMS-Like Tyrosine Kinase: Role in placenta accreta spectrum disorder

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