Arterial endothelial dysfunction in baboons fed a high-cholesterol, high-fat diet

Qiang Shi, Jane F. Vandeberg, Catherine Jett, Karen Rice, Michelle M. Leland, Leslie Talley, Rampratap S. Kushwaha, David L. Rainwater, John L. Vandeberg, Xing Li Wang

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    29 Scopus citations

    Abstract

    Background: Endothelial dysfunction signals the initiation and progression of atherosclerosis. Elevated LDL-cholesterol concentrations have been suggested to induce endothelial dysfunction, but direct in vivo evidence for the relation is still lacking. Objective: We examined the hypothesis that a high-cholesterol, high-fat (HCHF) diet can directly cause endothelial dysfunction in vivo. Design: We measured inflammatory and endothelial dysfunctional markers in circulating blood and directly in endothelial cells, which were collected by femoral artery biopsies, in 10 baboons before and after a 7-wk HCHF dietary challenge. Results: We found that the HCHF diet induced a high inflammatory status, as indicated by increased concentrations of interleukin 6, tumor necrosis factor α (TNF-α), and monocyte chemoattractant protein 1. Although the concentrations of endothelial dysfunctional markers, such as soluble vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1, were not increased by the HCHF diet, membrane-bound VCAM-1 and membrane-bound E-selectin on endothelial cells were highly increased after 7 wk of the HCHF diet (P < 0.01). In contrast, the concentrations of endothelial nitric oxide synthase in endothelial cells were significantly reduced by the 7-wk HCHF diet (P < 0.01). Furthermore, the dietary challenge attenuated endothelial cell responses to TNF-α, lipopolysaccharide, native LDL cholesterol, and oxidized LDL-cholesterol stimulation. Conclusions: Our results show that an HCHF diet can directly induce inflammation and endothelial dysfunction. Prior in vivo exposure to an HCHF diet attenuates the in vitro responses of endothelial cells to atherogenic risk factors. This preconditioning phenomenon may have significant clinical relevance.

    Original languageEnglish (US)
    Pages (from-to)751-759
    Number of pages9
    JournalAmerican Journal of Clinical Nutrition
    Volume82
    Issue number4
    Publication statusPublished - Dec 1 2005

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    Keywords

    • Endothelium
    • High-cholesterol
    • High-fat diet
    • Inflammation
    • Nonhuman primates

    ASJC Scopus subject areas

    • Medicine (miscellaneous)
    • Nutrition and Dietetics

    Cite this

    Shi, Q., Vandeberg, J. F., Jett, C., Rice, K., Leland, M. M., Talley, L., ... Wang, X. L. (2005). Arterial endothelial dysfunction in baboons fed a high-cholesterol, high-fat diet. American Journal of Clinical Nutrition, 82(4), 751-759.