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Arterial endothelial dysfunction in baboons fed a high-cholesterol, high-fat diet^1,2,3

¹ From the Departments of Genetics (QS, JFVB, CJ, DLR, and JLVB), Comparative Medicine (KR, MML, and LT), and Physiology and Medicine (RSK) and the Southwest National Primate Research Center (KR, MML, and JLVB), the Southwest Foundation for Biomedical Research, San Antonio, Texas, and the Division of Cardiothoracic Surgery, Michael E DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas (XLW)

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 (TNF-), 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-, 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.

Key Words: Nonhuman primates • endothelium • inflammation • high-cholesterol • high-fat diet

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				Q. Shi, G. B. Hubbard, R. S. Kushwaha, D. Rainwater, C. A. Thomas III, M. M. Leland, J. L. VandeBerg, and X. L. Wang Endothelial senescence after high-cholesterol, high-fat diet challenge in baboons Am J Physiol Heart Circ Physiol, June 1, 2007; 292(6): H2913 - H2920. [Abstract] [Full Text] [PDF]