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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2003;23:1358.)
© 2003 American Heart Association, Inc.

Vascular Biology

High Methionine and Cholesterol Diet Abolishes Endothelial Relaxation

Anthony Zulli; Robert E. Widdop; David L. Hare; Brian F. Buxton; M. Jane Black

From the Departments of Cardiac Surgery (A.Z., B.F.B.) and Cardiology (A.Z., D.L.H.), University of Melbourne, Austin Health, Heidelberg, and Departments of Pharmacology (R.E.W.) and Anatomy and Cell Biology (M.J.B.), Monash University, Clayton, Australia.

Correspondence to Dr Anthony Zulli, Division of Cardiovascular Research, Department of Cardiac Surgery, Austin Health, Heidelberg, Australia. E-mail az{at}austin.unimelb.edu.au

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.

Methods and 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.

Key Words: cholesterol • homocysteine • endothelial function • plaque • nitric oxide

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