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Differential effects of apoE3‐ and apoE4‐associated VLDL lipolysis products on monocyte activation
Author(s) -
Higgins Laura J,
Tetali Sarada D,
Rutledge John C
Publication year - 2008
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.22.1_supplement.1037.1
Subject(s) - lipolysis , postprandial , endocrinology , very low density lipoprotein , medicine , inflammation , monocyte , chemistry , apolipoprotein e , lipoprotein , cholesterol , adipose tissue , diabetes mellitus , disease
Atherosclerosis is an inflammatory condition perpetuated by the activation and recruitment of circulating monocytes. Postprandial lipemia, characterized by elevated triglyceride‐rich lipoproteins such as very low‐density lipoproteins (VLDL), has been implicated as a mechanism of chronic vascular injury. We hypothesized that postprandial VLDL lipolysis products (PVLP) would induce a greater inflammatory response from monocytes than fasting VLDL lipolysis products (FVLP), mediated by apoE isoform changes in the postprandial state. VLDL was isolated from human donors, subjected to lipolysis, and treated in combination with LPS on THP‐1 monocytes. We found that FVLP attenuated LPS‐induced TNFα secretion to a greater extent than PVLP. This was partially reversed by blocking apoE on FVLP, but not on PVLP. In addition, apoE3‐containing vesicles attenuated LPS‐induced TNFα and IL‐1β expression, while complexes with apoE4 increased cytokine expression. An apoE ELISA revealed that apoE3 binds to LPS with higher affinity than apoE4, suggesting that apoE3 can sequester LPS away from monocytes more readily, thus attenuating their activation. These results imply that postprandial changes in apoE structure and isoform on VLDL could have dramatic effects on vascular inflammation, with implications for atherogenesis. This work was supported by the Training Program in Biomolecular Technology (T32‐GM08799).