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• W2893637632 abstract "Abstract Background and aims Intrauterine growth restriction (IUGR) is a major risk factor for perinatal morbidity and mortality, leading to long-term adverse cardiovascular outcomes. The present study aimed to investigate the potential mechanisms in IUGR-associated vascular endothelial dysfunction. Methods and results Human umbilical vein endothelial cells (HUVECs) were derived from IUGR or normal newborns. We found that the proliferation of IUGR-derived HUVECs was accelerated compared to those from normal subjects. Gene profiles related to vascular function including vasomotion, oxidative stress, and angiogenesis were dysregulated in IUGR-HUVECs. Compared with HUVECs from normal newborns, nitric oxide (NO) production was reduced, with imbalance between endothelial nitric oxide synthase (eNOS) and arginase-2 (Arg-2) in IUGR. Meanwhile, intracellular asymmetric dimethylarginine (ADMA) level was elevated with diminished dimethylarginine dimethylaminohydrolase 1 (DDAH1) expression in IUGR-HUVECs. Furthermore, endothelin-1 (ET-1) and hypoxia-inducible factor 1α (HIF-1α) expression were increased, and endothelin receptor type-B (ETBR) was reduced in the IUGR group. IUGR-HUVECs exposed to hypoxia increased the ratio of ADMA to l -arginine, HIF-1α and protein arginine methyltransferase 1 (PRMT1) expression compared to controls. Conclusions The present study demonstrated that the reduction of NO bioavailability and release results from elevated Arg-2, accumulation of intracellular ADMA, and imbalance of ET-1 and ETBR, further leading to IUGR-associated vascular endothelial dysfunction. Our study provides novel evidence on the mechanism underlying fetal programming associated with IUGR, which will serve as potential therapeutic targets in the prevention of adverse cardiovascular consequences in adulthood." @default.
• W2893637632 created "2018-10-05" @default.
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• W2893637632 date "2018-12-01" @default.
• W2893637632 modified "2023-10-17" @default.
• W2893637632 title "Arginine bioavailability and endothelin-1 system in the regulation of vascular function of umbilical vein endothelial cells from intrauterine growth restricted newborns" @default.
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• W2893637632 doi "https://doi.org/10.1016/j.numecd.2018.09.002" @default.
• W2893637632 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30392707" @default.
• W2893637632 hasPublicationYear "2018" @default.
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