Plasma ceramide is increased and associated with proteinuria in women with pre-eclampsia and HELLP syndrome

Amraoui, Fouad; Lahsinoui, Hajar Hassani; Spijkers, Léon J. A.; Vogt, Liffert; Peters, Stephan L. M.; Wijesinghe, Dayanjan S.; Warncke, Urszula Osinska; Chalfant, Charles E.; Ris‐Stalpers, Carrie; Born, Bert‐Jan H. van den; Afink, Gijs B.

doi:10.1016/j.preghy.2019.12.006

Cited by 10 publications

(8 citation statements)

References 27 publications

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“…On the other hand, some pathogenic bacteria also have SMase D ( 66 , 67 ), which may stall wound healing independent of CERK, and thus, a combination therapy of 5-oxo-ETE and CERK inhibitors may provide more benefit in a clinical setting where the wound microbiome is also a major factor in wound healing outcomes. Lastly, a better mechanistic understanding of the CERK/5-oxo-ETE interplay could be valuable for treating other diseases highly correlated to these lipid biomarkers such as preeclampsia ( 68 , 69 ) and type 1 diabetes ( 70 , 71 ).…”

Section: Discussionmentioning

confidence: 99%

Ceramide kinase regulates acute wound healing by suppressing 5-oxo-ETE biosynthesis and signaling via its receptor OXER1

Maus

Stephenson

Ali

et al. 2022

Journal of Lipid Research

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Section: Discussionmentioning

confidence: 99%

Ceramide kinase regulates acute wound healing by suppressing 5-oxo-ETE biosynthesis and signaling via its receptor OXER1

Maus

Stephenson

Ali

et al. 2022

Journal of Lipid Research

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“…Phosphatase and tensin homolog (PTEN) inhibit the PI3K signaling pathway through dephosphorylation and inactivation of PIP3, ultimately suppressing the activation of AKT. [18][19][20] Considering the prominent role of hub genes in the metabolism pathways and genetic interaction networks, various molecular processes (regulation of DNA binding), some metabolism pathways (glycolysis/gluconeogenesis, placental, and pyruvate metabolism) or cellular signaling pathways (cAMP, Ras, Rap1, and protein kinase B signaling) can be traced through analyzing the hub genes in HELLP syndrome. 21,22 In this regard, molecular analysis has specifically identified the three metabolism pathways of pyruvate metabolism, TNF and FoxO signaling pathways, as the effective pathways in the pathogenesis of HELLP syndrome.…”

Section: Discussionmentioning

confidence: 99%

“…PIP3 relays the signal and activates the AKT (protein kinase B), which subsequently phosphorylates its targets and affects cell cycle and survival. Phosphatase and tensin homolog (PTEN) inhibit the PI3K signaling pathway through dephosphorylation and inactivation of PIP3, ultimately suppressing the activation of AKT 18–20 …”

Section: Discussionmentioning

confidence: 99%

Bioinformatics analysis of microarray data to identify hub genes, as diagnostic biomarker of HELLP syndrome: System biology approach

Asadikalameh

Maddah

Maleknia

et al. 2022

J of Obstet and Gynaecol

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Background: HELLP syndrome is one of the disorders characterized by hemolysis, increased liver enzymes and decreased platelet count. So far, many molecular pathways and genes have been identified in relation to the pathogenesis of this syndrome; however, the main cause of the incidence and progression of the disease has not been identified. Using the biological system approach is a way to target patients by identifying genes and molecular pathways. In this study, we investigated genes and important molecular factors in the pathogenesis of HELLP syndrome. Material and Methods: In this study, the microarray dataset was downloaded from Gene Expression Omnibus (GEO) database and analyzed using the GEO2R online tool for identifying differentially expressed genes (DEGs). Enrichment analysis of DEGs was evaluated using the Enrichr database. Then, protein-protein interaction (PPI) networks were constructed via the STRING database; they were visualized by Cytoscape. Then the STRING database was used to construct PPI networks. The hub genes were recognized using the cytoHubba. Ultimately, the interaction of the miRNA-hub genes and drug-hub genes were also evaluated. Result: After analysis, it was found that some genes with the highest degree of connectivity are involved in the pathogenesis of HELLP syndrome, which are known as the hub genes. These genes are as follows: KIT, JAK2, LEP, EP300, HIST1H4L, HIST1H4F, HIST1H4H, MMP9, THBS2, and ADAMTS3. Has-miR-34a-5p was also most associated with hub genes. Conclusion: Finally, it can be said, that the identification of genes and molecular pathways in HELLP syndrome can be helpful in identifying the pathogenesis pathways of the disease, and designing therapeutic targets.

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“…The associated mitochondrial dysfunction promotes cardiometabolic risk 101 and may provide a mechanistic explanation for their systemic metabolic effect. 102 The early role of ceramides in cardiometabolic risk may be best illustrated by the increased circulating levels and buildup in placental tissue in gestational diabetes, 103 preeclampsia, and HELLP (Hemolysis, Elevated Liver Enzymes and Low Platelets) syndrome, 104 maternal conditions that contribute to increased risk for lifelong cardiometabolic risk for both mother 105 and child. 106,107 Increased placental mitochondrial ceramide 16:0 in preeclampsia has mechanistically been linked to increased mitochondrial fission, fragmentation, and dysfunction.…”

Section: Sphingolipidsmentioning

confidence: 99%

Next Generation, Modifiable Cardiometabolic Biomarkers: Mitochondrial Adaptation and Metabolic Resilience: A Scientific Statement From the American Heart Association

Mietus-Snyder,

Perak,

Cheng

et al. 2023

Circulation

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Cardiometabolic risk is increasing in prevalence across the life span with disproportionate ramifications for youth at socioeconomic disadvantage. Established risk factors and associated disease progression are harder to reverse as they become entrenched over time; if current trends are unchecked, the consequences for individual and societal wellness will become untenable. Interrelated root causes of ectopic adiposity and insulin resistance are understood but identified late in the trajectory of systemic metabolic dysregulation when traditional cardiometabolic risk factors cross current diagnostic thresholds of disease. Thus, children at cardiometabolic risk are often exposed to suboptimal metabolism over years before they present with clinical symptoms, at which point life-long reliance on pharmacotherapy may only mitigate but not reverse the risk. Leading-edge indicators are needed to detect the earliest departure from healthy metabolism, so that targeted, primordial, and primary prevention of cardiometabolic risk is possible. Better understanding of biomarkers that reflect the earliest transitions to dysmetabolism, beginning in utero, ideally biomarkers that are also mechanistic/causal and modifiable, is critically needed. This scientific statement explores emerging biomarkers of cardiometabolic risk across rapidly evolving and interrelated “omic” fields of research (the epigenome, microbiome, metabolome, lipidome, and inflammasome). Connections in each domain to mitochondrial function are identified that may mediate the favorable responses of each of the omic biomarkers featured to a heart-healthy lifestyle, notably to nutritional interventions. Fuller implementation of evidence-based nutrition must address environmental and socioeconomic disparities that can either facilitate or impede response to therapy.

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Plasma ceramide is increased and associated with proteinuria in women with pre-eclampsia and HELLP syndrome

Cited by 10 publications

References 27 publications

Ceramide kinase regulates acute wound healing by suppressing 5-oxo-ETE biosynthesis and signaling via its receptor OXER1

Ceramide kinase regulates acute wound healing by suppressing 5-oxo-ETE biosynthesis and signaling via its receptor OXER1

Bioinformatics analysis of microarray data to identify hub genes, as diagnostic biomarker of HELLP syndrome: System biology approach

Next Generation, Modifiable Cardiometabolic Biomarkers: Mitochondrial Adaptation and Metabolic Resilience: A Scientific Statement From the American Heart Association

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