High methionine and cholesterol diet abolishes endothelial relaxation.
OBJECTIVE
High plasma cholesterol or homocysteine is a risk factor for atherosclerosis. Cholesterol and methionine, the precursor of homocysteine, are rarely eaten separately. Thus, the aims of this study were to determine neointima formation, aortic reactivity, and factors involved in endothelial function in rabbits fed high dietary cholesterol, methionine, or a combination of the two for 12 weeks.


RESULTS
Rabbit dietary groups were randomized into the following: control (Con), 0.5% cholesterol (Chol), 1% methionine (Meth), and 1% methionine+0.5% cholesterol (MethChol). Aortic reactivity was studied by isometric tension techniques, aortic volumetric analysis was determined by stereological techniques, and immunohistochemistry was used to localize endothelial and inducible NO synthases, superoxide dismutase, macrophages, and nitrotyrosine. Atherosclerosis was present in the Chol and MethChol groups. Endothelium-dependent relaxation was virtually abolished in the MethChol group compared with control. Such decrease in relaxation was not attributable to a vascular smooth muscle cell defect or to a decrease in endothelial NO synthase or superoxide dismutase content. Macrophages and inducible NO synthase immunoreactivity were present in Chol and MetChol groups.


CONCLUSIONS
The combination of high dietary cholesterol plus methionine virtually abolishes endothelium-dependent relaxation, underscoring the importance of multiple risk factors in the development of cardiovascular disease.
Zulli
Anthony
A
Department of Cardiac Surgery, University of Melbourne, Austin Health, Heidelberg, Australia. az@austin.unimelb.edu.au
Widdop
Robert E
RE
Hare
David L
DL
Buxton
Brian F
BF
Black
M Jane
MJ
D000818:Animals; D001012:Aorta, Abdominal / Q000473:pathology; D001161:Arteriosclerosis / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology*; D002784:Cholesterol / Q000097:blood; D002791:Cholesterol, Dietary / Q000008:administration & dosage / Q000009:adverse effects*; D008076:Cholesterol, HDL / Q000097:blood; D004730:Endothelium, Vascular / Q000503:physiopathology*; D006710:Homocysteine / Q000097:blood; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D008715:Methionine / Q000008:administration & dosage / Q000009:adverse effects*; D009131:Muscle, Smooth, Vascular / Q000503:physiopathology; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology; D011817:Rabbits; D014280:Triglycerides / Q000097:blood
D002791:Cholesterol, Dietary; D008076:Cholesterol, HDL; D014280:Triglycerides; D006710:Homocysteine; D010656:Phenylephrine; D002784:Cholesterol; D008715:Methionine; D019001:Nitric Oxide Synthase