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• W2574955539 endingPage "C516" @default.
• W2574955539 startingPage "C500" @default.
• W2574955539 abstract "Elevation of blood triglycerides, primarily as triglyceride-rich lipoproteins (TGRL), has been linked to cerebrovascular inflammation, vascular dementia, and Alzheimer’s disease (AD). Brain microvascular endothelial cells and astrocytes, two cell components of the neurovascular unit, participate in controlling blood-brain barrier (BBB) permeability and regulating neurovascular unit homeostasis. Our studies showed that infusion of high physiological concentrations of TGRL lipolysis products (TGRL + lipoprotein lipase) activate and injure brain endothelial cells and transiently increase the BBB transfer coefficient ( K i = permeability × surface area/volume) in vivo. However, little is known about how blood lipids affect astrocyte lipid accumulation and inflammation. To address this, we first demonstrated TGRL lipolysis products increased lipid droplet formation in cultured normal human astrocytes. We then evaluated the transcriptional pathways activated in astrocytes by TGRL lipolysis products and found upregulated stress and inflammatory-related genes including activating transcription factor 3 (ATF3), macrophage inflammatory protein-3α (MIP-3α), growth differentiation factor-15 (GDF15), and prostaglandin-endoperoxide synthase 2 (COX2). TGRL lipolysis products also activated the JNK/cJUN/ATF3 pathway, induced endoplasmic reticulum stress protein C/EBP homologous protein (CHOP), and the NF-κB pathway, while increasing secretion of MIP-3α, GDF15, and IL-8. Thus our results demonstrate TGRL lipolysis products increase the BBB transfer coefficient ( K i ), induce astrocyte lipid droplet formation, activate cell stress pathways, and induce secretion of inflammatory cytokines. Our observations are consistent with evidence for lipid-induced neurovascular injury and inflammation, and we, therefore, speculate that lipid-induced astrocyte injury could play a role in cognitive decline." @default.
• W2574955539 created "2017-01-26" @default.
• W2574955539 creator A5008505926 @default.
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• W2574955539 date "2017-04-01" @default.
• W2574955539 modified "2023-10-13" @default.
• W2574955539 title "Triglyceride-rich lipoprotein lipolysis products increase blood-brain barrier transfer coefficient and induce astrocyte lipid droplets and cell stress" @default.
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• W2574955539 doi "https://doi.org/10.1152/ajpcell.00120.2016" @default.
• W2574955539 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5407020" @default.
• W2574955539 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/28077357" @default.
• W2574955539 hasPublicationYear "2017" @default.
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