title: Arterial endothelial dysfunction in baboons fed a high-cholesterol, high-fat diet.
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.
  
  
  METHODS
  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.
authors.affiliation: Department of Genetics and the Southwest National Primate Research Center, the Southwest Foundation for Biomedical Research, San Antonio, Texas, USA.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Shi
authors.forename: Jane F
authors.initials: JF
authors.lastname: Vandeberg
authors.forename: Catherine
authors.initials: C
authors.lastname: Jett
authors.forename: Karen
authors.initials: K
authors.lastname: Rice
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Leland
authors.forename: Leslie
authors.initials: L
authors.lastname: Talley
authors.forename: Rampratap S
authors.initials: RS
authors.lastname: Kushwaha
authors.forename: David L
authors.initials: DL
authors.lastname: Rainwater
authors.forename: John L
authors.initials: JL
authors.lastname: Vandeberg
authors.forename: Xing Li
authors.initials: XL
authors.lastname: Wang
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D001706:Biopsy; D018932:Chemokine CCL2 / Q000378:metabolism; D002791:Cholesterol, Dietary / Q000008:administration & dosage / Q000494:pharmacology*; D004041:Dietary Fats / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D019040:E-Selectin / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology*; D005260:Female; D005263:Femoral Artery / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007249:Inflammation / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008055:Lipids / Q000097:blood; D008297:Male; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010215:Papio; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D015415:Biomarkers; D018932:Chemokine CCL2; D002791:Cholesterol, Dietary; D004041:Dietary Fats; D019040:E-Selectin; D018836:Inflammation Mediators; D015850:Interleukin-6; D008055:Lipids; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D019001:Nitric Oxide Synthase