title: Endothelial inflammation correlates with subject triglycerides and waist size after a high-fat meal.
abstract: A rise in postprandial serum triglycerides (PP-sTG) can potentiate inflammatory responses in vascular endothelial cells (ECs) and thus serves as an independent risk factor for predicting increased cardiovascular morbidity. We examined postprandial triglyceride-rich lipoproteins (PP-TGRLs) in subjects ranging from normal to hypertriglyceridemic for their capacity to alter EC acute inflammatory responses. Cultured human aortic ECs (HAECs) were conditioned with PP-TGRLs isolated from human serum at the peak after a moderately high-fat meal. VLDL particle size increased postprandially and varied directly with the subject's PP-sTG level and waist circumference. PP-TGRL particles bound to HAECs and were internalized via LDL receptor-mediated endocytosis. PP-TGRL alone did not induce an inflammatory response over the range of individuals studied. However, combined with low-dose TNF-α stimulation (0.3 ng/ml), it elicited a net 10-15% increase above cytokine alone in the membrane expression of VCAM-1, ICAM-1, and E-selectin, which was not observed with fasting TGRLs. In contrast to upregulation of ICAM-1 and E-selectin, VCAM-1 transcription and expression varied in direct proportion with individual PP-sTG and waist circumference. The extent of monocyte arrest on inflamed HAECs under shear stress also correlated closely with VCAM-1 expression induced by conditioning with PP-TGRL and TNF-α stimulation. This ex vivo approach provides a quantitative means to assess an individual's inflammatory potential, revealing a greater propensity for endothelial inflammation in hypertriglyceridemic individuals with abdominal obesity.
authors.affiliation: Department of Biomedical Engineering, University of California, Davis, California 95616, USA. agpasserini@ucdavis.edu
authors.forename: Ying I
authors.initials: YI
authors.lastname: Wang
authors.forename: John
authors.initials: J
authors.lastname: Schulze
authors.forename: Nadine
authors.initials: N
authors.lastname: Raymond
authors.forename: Tyler
authors.initials: T
authors.lastname: Tomita
authors.forename: Kayan
authors.initials: K
authors.lastname: Tam
authors.forename: Scott I
authors.initials: SI
authors.lastname: Simon
authors.forename: Anthony G
authors.initials: AG
authors.lastname: Passerini
mesh_terms: D001011:Aorta / Q000378:metabolism; D002478:Cells, Cultured; D004041:Dietary Fats / Q000378:metabolism*; D019040:E-Selectin / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008074:Lipoproteins / Q000097:blood / Q000378:metabolism*; D008297:Male; D009000:Monocytes / Q000378:metabolism; D056128:Obesity, Abdominal / Q000378:metabolism; D019518:Postprandial Period; D014280:Triglycerides / Q000097:blood / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D055105:Waist Circumference; D055815:Young Adult
chemical_list: D004041:Dietary Fats; D019040:E-Selectin; D008074:Lipoproteins; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; C030087:lipoprotein triglyceride; D018799:Intercellular Adhesion Molecule-1