A modified mouse model of instable carotid atherosclerotic plaque

Abstract

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.