Post-transcriptional down regulation of ICAM-1 in feto-placental endothelium in GDM

Díaz-Pérez, Francisca; Hiden, Ursula; Gauster, Martin; Lang, Ingrid; Kónya, Viktória; Heinemann, Ákos; Lögl, Jelena; Saffery, Richard; Desoyé, Gernot; Cvitic, Silvija

doi:10.1080/19336918.2015.1127467

Cited by 29 publications

(19 citation statements)

References 44 publications

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“…The pro-inflammatory cytokine TNFα activates NF-κB pathway [22], which subsequently upregulates ICAM-1 (intercellular adhesion molecule 1) expression [32]. TNFα is increased in cord blood when mothers are overweight [27], and fpEC also respond to TNFα with an induction of ICAM-1 expression [33]. Thus, we further tested whether hypoxia or TNFα reduce MME protein in fpEC in vitro.…”

Section: Discussionmentioning

confidence: 99%

Maternal Overweight Downregulates MME (Neprilysin) in Feto-Placental Endothelial Cells and in Cord Blood

Weiss

Berger

Brandl

et al. 2020

IJMS

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Maternal overweight in pregnancy alters the metabolic environment and generates chronic low-grade inflammation. This affects fetal development and programs the offspring’s health for developing cardiovascular and metabolic disease later in life. MME (membrane-metalloendopeptidase, neprilysin) cleaves various peptides regulating vascular tone. Endothelial cells express membrane-bound and soluble MME. In adults, the metabolic environment of overweight and obesity upregulates endothelial and circulating MME. We here hypothesized that maternal overweight increases MME in the feto-placental endothelium. We used primary feto-placental endothelial cells (fpEC) isolated from placentas after normal vs. overweight pregnancies and determined MME mRNA, protein, and release. Additionally, soluble cord blood MME was analyzed. The effect of oxygen and tumor necrosis factor α (TNFα) on MME protein in fpEC was investigated in vitro. Maternal overweight reduced MME mRNA (−39.9%, p < 0.05), protein (−42.5%, p = 0.02), and MME release from fpEC (−64.7%, p = 0.02). Both cellular and released MME protein negatively correlated with maternal pre-pregnancy BMI. Similarly, cord blood MME was negatively associated with pre-pregnancy BMI (r = −0.42, p = 0.02). However, hypoxia and TNFα, potential negative regulators of MME expression, did not affect MME protein. Reduction of MME protein in fpEC and in cord blood may alter the balance of vasoactive peptides. Our study highlights the fetal susceptibility to maternal metabolism and inflammatory state.

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Section: Discussionmentioning

confidence: 99%

Maternal Overweight Downregulates MME (Neprilysin) in Feto-Placental Endothelial Cells and in Cord Blood

Weiss

Berger

Brandl

et al. 2020

IJMS

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“…Diaz-Perez et al demonstrated a low expression level of both the cell adhesion molecule ICAM-1 in primary human fpEC and its soluble form in the supernatant of fpEC derived from four GDM women in respect to four CTRLs. Since miR-221 and miR-222 are two negative regulators of ICAM-1 [142,143] and are significantly upregulated in fpEC cells derived from GDM in respect to normal pregnancies, Diaz-Perez inferred that these microRNAs may determine the reduced ICAM-1 levels observed in the feto-placental endothelium in GDM [144]. Another study compared the microRNA expression in HUVECs derived from three infants from GDM women (IGDM) and from three infants from normoglycaemic CTRLs.…”

Section: Long-term Complicationsmentioning

confidence: 99%

Non-Coding RNA: Role in Gestational Diabetes Pathophysiology and Complications

Filardi

Catanzaro

Mardente

et al. 2020

IJMS

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Gestational Diabetes Mellitus (GDM) is defined as glucose intolerance that develops in the second or third trimester of pregnancy. GDM can lead to short-term and long-term complications both in the mother and in the offspring. Diagnosing and treating this condition is therefore of great importance to avoid poor pregnancy outcomes. There is increasing interest in finding new markers with potential diagnostic, prognostic and therapeutic utility in GDM. Non-coding RNAs (ncRNAs), including microRNAs, long non-coding RNAs and circular RNAs, are critically involved in metabolic processes and their dysregulated expression has been reported in several pathological contexts. The aberrant expression of several circulating or placenta-related ncRNAs has been linked to insulin resistance and β-cell dysfunction, the key pathophysiological features of GDM. Furthermore, significant associations between altered ncRNA profiles and GDM-related complications, such as macrosomia or trophoblast dysfunction, have been observed. Remarkably, the deregulation of ncRNAs, which might be linked to a detrimental intrauterine environment, can lead to changes in the expression of target genes in the offspring, possibly contributing to the development of long-term GDM-related complications, such as metabolic and cardiovascular diseases. In this review, all the recent findings on ncRNAs and GDM are summarized, particularly focusing on the molecular aspects and the pathophysiological implications of this complex relationship.

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“…Their levels are in an inverse relationship with maternal BMI. These proteins are markers of vascular inflammation (45). The low ICAM-1 protein levels in GDM can be regarded as an additional protective mechanism to avoid transmigration of fetal leukocytes into the subendothelial space of the fetoplacental circulation, thereby also contributing to reducing the risk of preatherosclerotic lesions.…”

Section: Preventing Impairment Of Fetoplacental Blood Flowdavoiding Pmentioning

confidence: 99%

The Human Placenta in Diabetes and Obesity: Friend or Foe? The 2017 Norbert Freinkel Award Lecture

Desoyé

2018

Diabetes Care

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The placenta plays a key role in sustaining fetal growth and development. Due to its position between mother and fetus, it is exposed to changes in the intrauterine environment in both circulations. The relative influence of changes in those circulations depends on the period of gestation. Early in pregnancy, maternal influences prevail and may affect the complex biological processes characteristic for this pregnancy period, such as placentation, early cell differentiation, and spiral artery remodeling. It is still unclear whether the placenta early in pregnancy is a friend or foe for the fetus. Later in pregnancy, when the fetal circulation is gradually establishing, fetal signals gain importance in regulating placental structure and function. Many of the placental alterations seen at term of pregnancy are the result of fetoplacental interactions often driven by fetal signals associated with maternal diabetes or obesity. These alterations, such as hypervascularization or enhanced cholesterol removal from placental endothelial cells, can be regarded as adaptations to maintain homeostasis at the fetoplacental interface and, thus, to protect the fetus. However, extreme conditions such as poorly controlled diabetes or pronounced obesity may exceed placental homeostatic capacity, with potentially adverse consequences for the fetus. Thus, in late pregnancy, the placenta acts mostly as a friend as long as the environmental perturbations do not exceed placental capacity for mounting adaptive responses.

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Post-transcriptional down regulation of ICAM-1 in feto-placental endothelium in GDM

Cited by 29 publications

References 44 publications

Maternal Overweight Downregulates MME (Neprilysin) in Feto-Placental Endothelial Cells and in Cord Blood

Maternal Overweight Downregulates MME (Neprilysin) in Feto-Placental Endothelial Cells and in Cord Blood

Non-Coding RNA: Role in Gestational Diabetes Pathophysiology and Complications

The Human Placenta in Diabetes and Obesity: Friend or Foe? The 2017 Norbert Freinkel Award Lecture

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