Triglyceride-rich lipoproteins prime aortic endothelium for an enhanced inflammatory response to tumor necrosis factor-alpha.
High levels of triglyceride-rich lipoproteins (TGRLs) in blood are linked to development of atherosclerosis, yet the mechanisms by which these particles initiate inflammation of endothelium are unknown. TGRL isolated from human plasma during the postprandial state was examined for its capacity to bind to cultured human aortic endothelial cells (HAECs) and alter the acute inflammatory response to tumor necrosis factor-alpha. HAECs were repetitively incubated with dietary levels of freshly isolated TGRL for 2 hours per day for 1 to 3 days to mimic postprandial lipidemia. TGRL induced membrane upregulation of the low-density lipoprotein family receptors LRP and LR11, which was inhibited by the low-density lipoprotein receptor-associated protein-1. TGRLs alone did not elicit inflammation in HAECs but enhanced the inflammatory response via a 10-fold increase in sensitivity to cytokine stimulation. This was reflected by increased mitogen-activated protein kinase activation, nuclear translocation of NF-kappaB, amplified expression of endothelial selectin and VCAM-1, and a subsequent increase in monocyte-specific recruitment under shear flow as quantified in a microfabricated vascular mimetic device.
Ting
Harold J
HJ
Department of Biomedical Engineering, University of California, Davis, Genome and Biomedical Sciences Facility, Davis, CA 95616-5294, USA.
Stice
James P
JP
Schaff
Ulrich Y
UY
Hui
David Y
DY
Rutledge
John C
JC
Knowlton
Anne A
AA
Passerini
Anthony G
AG
Simon
Scott I
SI
D001011:Aorta; D001018:Aortic Diseases / Q000209:etiology*; D053305:Apolipoprotein C-III / Q000378:metabolism / Q000494:pharmacology; D001161:Arteriosclerosis / Q000209:etiology*; D001167:Arteritis / Q000209:etiology*; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D002914:Chylomicrons / Q000097:blood; D004041:Dietary Fats / Q000008:administration & dosage / Q000009:adverse effects*; D019040:E-Selectin / Q000096:biosynthesis / Q000235:genetics; D004705:Endocytosis; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology; D005217:Fat Emulsions, Intravenous / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D015228:Hypertriglyceridemia / Q000097:blood / Q000150:complications*; D007003:Hypoglycemia; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000235:genetics; D026563:LDL-Receptor Related Protein-Associated Protein / Q000494:pharmacology; D026502:LDL-Receptor Related Proteins / Q000187:drug effects / Q000378:metabolism*; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology; D008075:Lipoproteins, HDL / Q000097:blood / Q000633:toxicity*; D008077:Lipoproteins, LDL / Q000097:blood / Q000633:toxicity*; D008079:Lipoproteins, VLDL / Q000097:blood / Q000633:toxicity*; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000187:drug effects / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000187:drug effects / Q000378:metabolism*; D008955:Models, Cardiovascular; D009000:Monocytes / Q000166:cytology / Q000187:drug effects; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress; D011973:Receptors, LDL / Q000187:drug effects / Q000378:metabolism*; D012212:Rheology; D015398:Signal Transduction / Q000187:drug effects; D014280:Triglycerides / Q000097:blood / Q000633:toxicity*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology* / Q000502:physiology; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis / Q000235:genetics; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D053305:Apolipoprotein C-III; D015815:Cell Adhesion Molecules; D002914:Chylomicrons; D004041:Dietary Fats; D019040:E-Selectin; D005217:Fat Emulsions, Intravenous; C034396:HDL-triglyceride; D026563:LDL-Receptor Related Protein-Associated Protein; D026502:LDL-Receptor Related Proteins; D008070:Lipopolysaccharides; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D026901:Membrane Transport Proteins; D016328:NF-kappa B; D011973:Receptors, LDL; C102582:SORL1 protein, human; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; C036053:VLDL receptor; D019010:Vascular Cell Adhesion Molecule-1; C032607:low density lipoprotein triglyceride; C030106:very low density lipoprotein triglyceride; D018799:Intercellular Adhesion Molecule-1; D048051:p38 Mitogen-Activated Protein Kinases