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

Am J Clin Nutr. 2005 Oct;82(4):751-9. doi: 10.1093/ajcn/82.4.751.

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 alpha (TNF-alpha), 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-alpha, 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Biomarkers / blood
  • Biomarkers / metabolism
  • Biopsy
  • Chemokine CCL2 / metabolism
  • Cholesterol, Dietary / administration & dosage
  • Cholesterol, Dietary / pharmacology*
  • Dietary Fats / administration & dosage
  • Dietary Fats / pharmacology*
  • Disease Models, Animal
  • E-Selectin / metabolism
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / physiopathology*
  • Female
  • Femoral Artery / drug effects
  • Femoral Artery / metabolism
  • Femoral Artery / pathology
  • Inflammation / metabolism*
  • Inflammation Mediators / metabolism
  • Interleukin-6 / metabolism
  • Lipids / blood
  • Male
  • Nitric Oxide Synthase / metabolism
  • Papio
  • Tumor Necrosis Factor-alpha / metabolism
  • Vascular Cell Adhesion Molecule-1 / metabolism

Substances

  • Biomarkers
  • Chemokine CCL2
  • Cholesterol, Dietary
  • Dietary Fats
  • E-Selectin
  • Inflammation Mediators
  • Interleukin-6
  • Lipids
  • Tumor Necrosis Factor-alpha
  • Vascular Cell Adhesion Molecule-1
  • Nitric Oxide Synthase