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(Circulation Research. 2007;100:381.)
© 2007 American Heart Association, Inc.

Molecular Medicine

Triglyceride-Rich Lipoproteins Prime Aortic Endothelium for an Enhanced Inflammatory Response to Tumor Necrosis Factor-

Harold J. Ting, James P. Stice, Ulrich Y. Schaff, David Y. Hui, John C. Rutledge, Anne A. Knowlton, Anthony G. Passerini, Scott I. Simon

From the Departments of Biomedical Engineering (H.J.T., U.Y.S., A.G.P., S.I.S.) and Cardiovascular Medicine (J.P.S., J.C.R., A.A.K.), University of California, Davis; and Department of Pathology (D.Y.H.), University of Cincinnati, Ohio.

Correspondence to Dr Scott I. Simon, Department of Biomedical Engineering, University of California, Davis, 451 E Health Sciences Dr, Genome and Biomedical Sciences Facility, Davis, CA 95616-5294. E-mail sisimon{at}ucdavis.edu

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-. 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-B, 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.

Key Words: triglyceride-rich lipoprotein • endothelium • monocyte • NFB • vascular adhesion molecule-1 • atherosclerosis

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