Hyperglycemia disturbs trophoblast functions and subsequently leads to failure of uterine spiral artery remodeling

Zhu, Yueyue; Liu, Xiaorui; Xu, Yichi; Lin, Yi

doi:10.3389/fendo.2023.1060253

Cited by 4 publications

(1 citation statement)

References 125 publications

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“…There is a compelling evidence suggesting that hyperglycemia can lead to immune dysfunction ( 46 ), abnormal ratios of immune cells, altered secretion of cytokines, and an inflammatory state, thereby rendering the patient more susceptible to infection and related comorbidities ( 47 , 48 ). Maternal hyperglycemia may trigger a “glucose stress” response and systemic inflammatory response, including changes in the infiltration, differentiation, and activation of maternal innate and adaptive immune cells ( 49 ). Moreover, cytokine expressions at the maternal-fetal interface also changed a lot under a high glucose environment, including an increase of IL-4, IL-6, IL-10, IL-17, and IFN-γ and a decrease of IL-1β and IL-8 ( 50 ).…”

Section: Discussionmentioning

confidence: 99%

Aberrant NK cell profile in gestational diabetes mellitus with fetal growth restriction

Xiong,

Wang,

et al. 2024

Front. Immunol.

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Gestational diabetes mellitus (GDM) is a gestational disorder characterized by hyperglycemia, that can lead to dysfunction of diverse cells in the body, especially the immune cells. It has been reported that immune cells, specifically natural killer (NK) cells, play a crucial role in normal pregnancy. However, it remains unknown how hyperglycemia affects NK cell dysfunction thus participates in the development of GDM. In this experiment, GDM mice were induced by an intraperitoneal injection of streptozotocin (STZ) after pregnancy and it has been found that the intrauterine growth restriction occurred in mice with STZ-induced GDM, accompanied by the changed proportion and function of NK cells. The percentage of cytotoxic CD27-CD11b+ NK cells was significantly increased, while the proportion of nourished CD27-CD11b- NK cells was significantly reduced in the decidua of GDM mice. Likewise, the same trend appeared in the peripheral blood NK cell subsets of GDM patients. What’s more, after intrauterine reinfusion of NK cells to GDM mice, the fetal growth restriction was alleviated and the proportion of NK cells was restored. Our findings provide a theoretical and experimental basis for further exploring the pathogenesis of GDM.

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Section: Discussionmentioning

confidence: 99%

Aberrant NK cell profile in gestational diabetes mellitus with fetal growth restriction

Xiong,

Wang,

et al. 2024

Front. Immunol.

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ARID1A recruits GATA2 to regulate the senescence of trophoblast cells under high-glucose condition

Huang,

Yang,

Wang

et al. 2024

Placenta

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Integrative analysis of gene expression, protein abundance, and metabolomic profiling elucidates complex relationships in chronic hyperglycemia-induced changes in human aortic smooth muscle cells

Bohara,

Bagheri,

Ertugral

et al. 2024

J Biol Eng

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Type 2 diabetes mellitus (T2DM) is a major public health concern with significant cardiovascular complications (CVD). Despite extensive epidemiological data, the molecular mechanisms relating hyperglycemia to CVD remain incompletely understood. We here investigated the impact of chronic hyperglycemia on human aortic smooth muscle cells (HASMCs) cultured under varying glucose conditions in vitro, mimicking normal (5 mmol/L), pre-diabetic (10 mmol/L), and diabetic (20 mmol/L) conditions, respectively. Normal HASMC cultures served as baseline controls, and patient-derived T2DM-SMCs served as disease controls. Results showed significant increases in cellular proliferation, area, perimeter, and F-actin expression with increasing glucose concentration ( p < 0.01), albeit not exceeding the levels in T2DM cells. Atomic force microscopy analysis revealed significant decreases in Young’s moduli, membrane tether forces, membrane tension, and surface adhesion in SMCs at higher glucose levels ( p < 0.001), with T2DM-SMCs being the lowest among all the cases ( p < 0.001). T2DM-SMCs exhibited elevated levels of selected pro-inflammatory markers (e.g., ILs-6, 8, 23; MCP-1; M-CSF; MMPs-1, 2, 3) compared to glucose-treated SMCs ( p < 0.01). Conversely, growth factors (e.g., VEGF-A, PDGF-AA, TGF-β1) were higher in SMCs exposed to high glucose levels but lower in T2DM-SMCs ( p < 0.01). Pathway enrichment analysis showed significant increases in the expression of inflammatory cytokine-associated pathways, especially involving IL-10, IL-4 and IL-13 signaling in genes that are up-regulated by elevated glucose levels. Differentially regulated gene analysis showed that compared to SMCs receiving normal glucose, 513 genes were upregulated and 590 genes were downregulated in T2DM-SMCs; fewer genes were differentially expressed in SMCs receiving higher glucose levels. Finally, the altered levels in genes involved in ECM organization, elastic fiber synthesis and formation, laminin interactions, and ECM proteoglycans were identified. Growing literature suggests that phenotypic switching in SMCs lead to arterial wall remodeling (e.g., change in stiffness, calcific deposits formation), with direct implications in the onset of CVD complications. Our results suggest that chronic hyperglycemia is one such factor that leads to morphological, biomechanical, and functional alterations in vascular SMCs, potentially contributing to the pathogenesis of T2DM-associated arterial remodeling. The observed differences in gene expression patterns between in vitro hyperglycemic models and patient-derived T2DM-SMCs highlight the complexity of T2DM pathophysiology and underline the need for further studies. Supplementary Information The online version contains supplementary material available at 10.1186/s13036-024-00457-w.

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Hyperglycemia disturbs trophoblast functions and subsequently leads to failure of uterine spiral artery remodeling

Cited by 4 publications

References 125 publications

Aberrant NK cell profile in gestational diabetes mellitus with fetal growth restriction

Aberrant NK cell profile in gestational diabetes mellitus with fetal growth restriction

ARID1A recruits GATA2 to regulate the senescence of trophoblast cells under high-glucose condition

Integrative analysis of gene expression, protein abundance, and metabolomic profiling elucidates complex relationships in chronic hyperglycemia-induced changes in human aortic smooth muscle cells

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