The Expression Of Matrix Metalloproteinase-9, Tissue Inhibitor Of Metalloproteinase-1 And Vascular Endothelial Growth Factor In Rabbit Carotid Artery Plaque And The Relationship Between Plaque Neovascularization

Objective:To detect the expressions of matrix metalloproteinase 9(MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1) and vascular endothelial growth factor (VEGF) in the Rabbit carotid artery plaque and to explore the relationship between plaque neovascularization.Methods:Forty male New Zealand white rabbits were randomly divided into 4 groups:Group A (the blank control group),group B (hypsocholesterol diet group),group C (silicone collar intervention and hypsocholesterol diet for 14 days group),group D (silicone collar intervention and hypsocholesterol diet for 28 days group). On the 14th and 28th day, observations were made of the formation of carotid artery plaque and the changes in plaque neovascularization through ultrasound imaging examination; Pathologic changes were evaluated by the way of immunohistochemistry with hematoxylin and eosin stain. The expressions of MMP-2, RAM-11 and CD31 were detected by immunohistochemistry. Finally, the correlations between the mean optical density (MOD) of the positive cells and indexes of neovascularization were analyzed among each group.Results:Group C and group D had the formation of plaque and new blood vessels; group A and group B had no plaque formation; Immunohistochemistry proved that there existed notable difference between group C and group D in MMP-9/TIMP-1, VEGF, and CD31 (P <0.05). Compared with group C, the expression of MMPs in group D increased and TIMP-1 decreased without significant statistical difference(P>0.05). Correlation analysis showed that MMP-9/TIMP-1, VEGF and angiogenesis were positively related (P<0.01).Conclusion:1.The rabbit carotid atherosclerotic model can be successfully induced by silicone collar intervention and hypsocholesterol diet;2.Rabbit carotid artery plaque angiogenesis in the early stage;3.Contrast-enhanced Ultrasound can detect dynamic changes of the neovascularizations in rabbit carotid atherosclerotic plaques;4.The increase of MMP-9/TIMP-1 ratio and the enhanced expression of VEGF correlate with the Neovascularization within carotid plaques and play an important role in the development of plaques.