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Triglyceride‐rich lipoproteins prime aortic endothelium for an enhanced inflammatory response to TNF‐α
Author(s) -
Ting Harold Jean,
Knowlton Anne A,
Passerini Anthony G.,
Simon Scott I
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a700-d
Subject(s) - postprandial , chylomicron , inflammation , tumor necrosis factor alpha , selectin , endothelium , cytokine , medicine , immunology , endocrinology , lipoprotein , biology , cholesterol , diabetes mellitus , very low density lipoprotein
Background‐ High levels of triglyceride‐rich lipoproteins (TGRL) 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 human aortic endothelial cells (HAEC) and alter the acute inflammatory response to tumor necrosis factor (TNF)‐α. Methods and Results‐ HAEC were repetitively incubated with TGRL for 2 hours per day for 1–3 days to mimic postprandial lipidemia. TGRL induced membrane upregulation of the LDL family receptors LRP and LR11, which was inhibited by the LDL receptor‐associated protein (RAP)‐1. TGRL treatment alone did not elicit inflammation in HAEC, but enhanced the response to TNF‐α; reflected by increased MAP kinase activation, nuclear translocation of NFκB, amplified expression of E‐selectin and VCAM‐1, and a subsequent increase in monocyte‐specific recruitment under shear flow. Conclusions‐ Repetitive exposure of HAEC to dietary levels of native TGRL enhanced the inflammatory response via a 10‐fold drop in the threshold for cytokine stimulation leading to a doubling in the recruitment efficiency of monocytes observed in a microfabricated vascular mimetic device. This work was supported by National Institutes of Health grants AI47294 (SIS), HL077281 and AG19327 (AK).