title: Dietary reversal of experimental hypercholesterolemia improves endothelial dysfunction of epicardial arteries but not of small coronary vessels in pigs.
abstract: Endothelial dysfunction is characterized by impaired vasodilation, increase of oxidative stress and inflammation. The current study was designed to test the hypothesis that reversal of hypercholesterolemic diet alone does not normalize all the parameters of endothelial dysfunction. After 10 weeks on a high-cholesterol diet, female juvenile pigs were randomized to normal diet (n=5, "Reversals") or continued on the same diet (n=6, "HC") for another 6 weeks. A control group of 11 pigs received a normal diet ("C"). Coronary epicardial and arteriolar endothelial function was tested in vitro. NFkappaB and p47phox expression was analyzed in epicardial arteries and myocardium, respectively. P47phox localization in coronary arteries was demonstrated with immunohistochemistry. Lipid levels normalized in Reversal pigs. Epicardial arteries of Reversals showed a normalized relaxation and NFkappaB expression compared to HC (p<0.05). Small vessel relaxation remained attenuated, and expression of p47phox in myocardial tissue was elevated in Reversals compared to C (p<0.05). Dietary lowering of serum cholesterol and LDL improves vascular function of epicardial arteries but neither of small vessels nor vascular oxidative stress within this time frame. Hence, dietary normalization of serum lipid levels alone may not be synonymous to normalization of the components of endothelial dysfunction.
authors.affiliation: Division of Cardiovascular Diseases, Mayo Clinic College of Medicine, Rochester, MN, USA.
authors.forename: Katherine J E
authors.initials: KJ
authors.lastname: Sattler
authors.forename: Offer
authors.initials: O
authors.lastname: Galili
authors.forename: Martin
authors.initials: M
authors.lastname: Rodriguez-Porcel
authors.forename: James D
authors.initials: JD
authors.lastname: Krier
authors.forename: Lilach O
authors.initials: LO
authors.lastname: Lerman
authors.forename: Amir
authors.initials: A
authors.lastname: Lerman
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D003331:Coronary Vessels / Q000378:metabolism / Q000503:physiopathology*; D006152:Cyclic GMP / Q000378:metabolism; D004036:Diet, Atherogenic; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D006937:Hypercholesterolemia / Q000178:diet therapy*; D007150:Immunohistochemistry; D019255:NADPH Oxidases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D013482:Superoxide Dismutase / Q000097:blood; D034421:Sus scrofa
chemical_list: D016328:NF-kappa B; D013482:Superoxide Dismutase; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; D006152:Cyclic GMP