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Binding of triglyceride rich lipoproteins to LDL receptor amplifies inflammatory responses of aortic endothelium.
Author(s) -
Ting Harold Jean,
Powers Andrew,
Rutledge John C,
Simon Scott I
Publication year - 2006
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.20.4.a206-b
Subject(s) - lipoprotein , endothelium , inflammation , apolipoprotein b , receptor , endocrinology , medicine , selectin , chemistry , immunology , cholesterol , biology
Recent discoveries have led to the recognition of atherosclerosis as an inflammatory disease consisting of elements similar to established autoimmune disorders. Triglyceride rich lipoproteins (TGRL) are elaborated during the postprandial state and give rise to remnant particles known to be a risk factor for atherosclerosis. We have developed a model of repetitive injury wherein human aortic endothelial cells (HAEC) were repetitively exposed to human TGRL freshly isolated from plasma following consumption of a 30% fat meal. Preincubation over 3 days with TGRL was not itself inflammatory, but in conjunction with acute stimulation, upregulated VCAM‐1 and E‐selectin expression up to 2‐fold that of HAEC stimulated by TNF‐alpha alone. Monocyte adhesion in shear flow to a HAEC monolayer, which formed the substrate of a parallel plate flow chamber, also increased by 1–2 fold in response to repetitive injury with TGRL followed by acute stimulation. This increased adhesive efficiency was specific for monocytes, as neutrophil adhesion was not significantly affected by TGRL preincubation. HAEC activation involved binding of TGRL to the vLDL receptor LR11 and this was blocked by co‐incubation with receptor‐associated protein (RAP), a high affinity inhibitor of the LDL receptor‐related protein (LRP) and a low affinity inhibitor of the LDL receptor. This repetitive injury model reveals events linking apolipoprotein binding and inflammation of aortic endothelium, crucial to elucidating lesion pathology. This study supported by NIH R01‐AI47294.