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 stereological 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.