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Publication
Triglyceride-rich lipoprotein lipolysis products increase blood-brain barrier
transfer coefficient and induce astrocyte lipid droplets and cell stress.
Authors Lee LL, Aung HH, Wilson DW, Anderson SE, Rutledge JC, Rutkowsky JM
Submitted By Jennifer Rutkowsky on 1/18/2017
Status Published
Journal American journal of physiology. Cell physiology
Year 2017
Date Published
Volume : Pages Not Specified : Not Specified
PubMed Reference 28077357
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 increases the BBB transfer
coefficient (Ki=permeability x 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 up-regulated stress and inflammatory-related genes including
activating transcription factor 3 (ATF3), macrophage inflammatory protein-3a
(MIP-3a), growth differentiation factor-15 (GDF15), and
prostaglandin-endoperoxide synthase 2 (COX2). TGRL lipolysis products also
activated the JNK/cJUN/ATF3 pathway, induced ER stress protein CHOP, and the
NF?B pathway, while increasing secretion of MIP-3a, GDF15, and IL-8. Thus, our
results demonstrate TGRL lipolysis products increase the BBB transfer
coefficient (Ki), 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.






Genes
SymbolDescription
Ldlrlow density lipoprotein receptor

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