Abstract:

Objective To induce vulnerable aortic plaque model in atherosclerosis of homocysteine by 2% (wt/vol) L-methionine in ApoE gene knockout mice. Methods Sixty 6-week old C57BL/6J ApoE gene knockout mice were randomly divided into three groups, with 20 rats in each group. Same amount of drinking water was administered to rats in control group, rats in high methionine group were intragastrically administrated with 2%(wt/vol) L-methionine, and those in extremely higher methionine group were intragastrically administrated with 3%(wt/vol) L-methionine. Besides, another 20 normal rats were served as normal control group. Serum homocysteine and lipid changes were detected one month and two months later, and the changes of plaque size, thickness of fibrous cap, collagen ratio and inflammatory infiltration degree were measured by HE, EVG elastic fiber staining and collagen staining of plaque and anti-MAC3 monoclonal antibody labeling. Cell apoptosis in aortic tissues was determined by TUNEL method. Results High methionine dose-dependently and time-dependently induced the development of vulnerable aortic plaque in atherosclerosis in ApoE gene knockout mice. Vascular smooth muscle cells exhibited  increasement of vacuole and lysome, dilatation of endoplasmic reticulum and deformation of mitochondria. The endothelial cells were edematous and deforming. The apoptosis cells existed simultaneously in the lipid core. Conclusion High methionine diet could induce hyperhomocysteinemia in ApoE gene knockout mice, which may promote the development of vulnerable plaque in atherosclerosis. Proliferation and apoptosis of vascular smooth muscle cells coexisted in plaque.

Key words: homocysteine, methionine, ApoE gene, atherosclerosis