High dietary methionine plus cholesterol exacerbates atherosclerosis formation in the left main coronary artery of rabbits

Although mild hyperhomocysteinemia is a risk factor for cardiovascular events and mortality, there is no evidence to suggest that mild hyperhomocysteinemia stimulates coronary artery atherosclerosis formation. Objective: To compare the development of coronary artery atherosclerosis in rabbits following the induction of hyperhomocysteinemia and hypercholesterolemia through diet, and whether the combination of these risk factors exacerbated atherosclerosis formation. Methods: New Zealand White rabbits were fed for 12 weeks either a control diet, a 1% methionine diet (Meth), a 0.5% cholesterol diet (Chol) or the combination of the two diets (MethChol). Using volumetric stereo-logical techniques, we quantitated the volume of intima, media and lumen of the left main coronary artery (LMCA). Results: Atherosclerosis was present in the Chol group, and increased in the MethChol group. There was no atherosclerosis in the control or Meth groups. Conclusions: These results underscore the difference in the atherogenicity of hypercholesterolemia alone and mild hyperhomocysteinemia alone. Thus, we suggest that isolated mild hyperhomocysteinemia is not a risk factor for the initiation of coronary artery atherosclerosis formation over a short period of time, but may act in conjunction with other risk factors to further increase plaque formation. (C) 2004 Elsevier Ireland Ltd. All rights reserved.