Objective: To explore a modified method for constructing a mouse model of instable carotid plaque and provide the mouse model for simulating the development of human instable carotid plaque. Methods: Twenty-four
low density lipoprotein receptor deficiency (LDLr-/-), C57BL/6, male mice were randomized into two groups according to computer-generated table, tandem constriction of carotid artery+ high
cholesterol diet (tandem surgery group, n=12);
sham surgery+ high
cholesterol diet(
sham surgery group, n=12). After 12 weeks of consecutive feeding, murine carotid artery were collected and analyzed by carotid ultrasound, pathological examination to assess the formation and stability of
atherosclerotic plaque. Results: No statistical difference in
body weight and blood
lipid level between the two groups was observed (all P>0.05). After surgery, through ultrasound biomicroscopy, obvious
stenosis at the two sites of tandem constriction and
atherosclerotic plaque between the two sites were observed in tandem surgery group. By pathological examination, no plaque was formed in carotid artery in
sham surgery group. The
lipid area in the stable plaque of innominate artery in
sham surgery group and the plaque of carotid artery in tandem surgery group were (4.8±0.6) ×10(4),(10.2±1.1)×10(4) μm(2), respectively. The difference was statistically significant between the two groups (t=12.023,P<0.001). In addition, the thickness of fibrous cap in the above groups were (122.4±17.8), (41.3±20.2) μm, respectively. The difference was statistically significant either (t=9.224, P<0.001). The region of necrotic core were (3.3±0.4)×10(4),(8.1±0.9)×10(4) μm(2).The difference was statistically significant as well (t=13.456, P<0.001). The percentage of macrophages in innominate artery of
sham surgery group and in carotid artery of tandem surgery group were (20.8±5.2)%, (38.6±6.4)%, respectively.The percentage of vascular smooth muscle cells were (32.5±7.3)%,(21.2±5.1)%, respectively (t=6.114,3.585, all P<0.05). The results indicated that the plaque in tandem surgery group had severer inflammatory response. Conclusion: Through tandem constriction surgery upon carotid artery in
LDL-/-mouse, instable carotid
atherosclerotic plaque can be induced, which is less time-consuming, replicable and effective.