The atherogenic effect of excess methionine intake
- 9 December 2003
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 100 (25), 15089-15094
- https://doi.org/10.1073/pnas.2436385100
Abstract
Methionine is the precursor of homocysteine, a sulfur amino acid intermediate in the methylation and transsulfuration pathways. Elevated plasma homocysteine (hyperhomocysteinemia) is associated with occlusive vascular disease. Whether homocysteine per se or a coincident metabolic abnormality causes vascular disease is still an open question. Animals with genetic hyperhomocysteinemia have so far not displayed atheromatous lesions. However, when methionine-rich diets are used to induce hyperhomocysteinemia, vascular pathology is often observed. Such studies have not distinguished the effects of excess dietary methionine from those of hyperhomocysteinemia. We fed apolipoprotein E-deficient mice with experimental diets designed to achieve three conditions: (i) high methionine intake with normal blood homocysteine; (ii) high methionine intake with B vitamin deficiency and hyperhomocysteinemia; and (iii) normal methionine intake with B vitamin deficiency and hyperhomocysteinemia. Mice fed methionine-rich diets had significant atheromatous pathology in the aortic arch even with normal plasma homocysteine levels, whereas mice fed B vitamin-deficient diets developed severe hyperhomocysteinemia without any increase in vascular pathology. Our findings suggest that moderate increases in methionine intake are atherogenic in susceptible mice. Although homocysteine may contribute to the effect of methionine, high plasma homocysteine was not independently atherogenic in this model. Some product of excess methionine metabolism rather than high plasma homocysteine per se may underlie the association of homocysteine with vascular disease.Keywords
This publication has 68 references indexed in Scilit:
- Plasma Homocysteine As a Cardiovascular Risk Factor: Causal, Consequential, or of No Consequence?Nutrition Reviews, 2009
- Total plasma homocysteine level and risk of cardiovascular disease: A meta-analysis of prospective cohort studiesJournal of Clinical Epidemiology, 2002
- Expression of Interleukin-6 in Atherosclerotic Lesions of Male ApoE-Knockout MiceArteriosclerosis, Thrombosis, and Vascular Biology, 1998
- A Definition of Advanced Types of Atherosclerotic Lesions and a Histological Classification of AtherosclerosisArteriosclerosis, Thrombosis, and Vascular Biology, 1995
- Increased Plasma and Lipoprotein Lipid Peroxidation in apo E-Deficient MiceBiochemical and Biophysical Research Communications, 1994
- Atherosclerosis in mice lacking apo E. Evaluation of lesional development and progression.Arteriosclerosis and Thrombosis: A Journal of Vascular Biology, 1994
- Spontaneous Hypercholesterolemia and Arterial Lesions in Mice Lacking Apolipoprotein EScience, 1992
- Severe hypercholesterolemia and atherosclerosis in apolipoprotein E-deficient mice created by homologous recombination in ES cellsCell, 1992
- Experimental Homocystinemia, Endothelial Lesions and ThrombosisJournal of Vascular Research, 1979
- Activation of cystathionine synthase by adenosylmethionine and adenosylethionineBiochemical and Biophysical Research Communications, 1975