Expression And Significance Of Cyclooxygenase-2 And Matrix Metalloproteinase-13 In Human Coronary Atherosclerotic Plaque

Background: Acute coronary syndrome is due to the rupture of coronary atherosclerotic plaque,which trigger thrombosis in coronary artery.The patient show a series of clinical symptoms which include unstable angina,acute myocardial infarction(AMI)and the electrocardiogram T wave changes in electrocardiogram.There is a close correlation between COX-2 and the malignant tumors occurrence,invasion,metastasis and prognosis,such as lung cancer,breast cancer,gastric cancer,prostate cancer,cervical cancer,etc.In recent years,COX-2 was concerned for inducing,aggravating inflammation,promoting plaque rupture and inducing ACS.MMP-13 is one of the members of the matrix metalloproteinase family,its substrate is very wide,include almost all components of extracellular matrix and basement membrane.So it may participate in the weakening of the fibrous cap to promote the plaque rupture.Purpose: In this study,we detected the expression of COX-2,MMP-13,CD131,CD68 and actin by immunohistochemistry in normal and AS coronary artery.We check the expression of COX-2 and MMP-13 positioning with CD68 and actin.CD131 is used to mark the new blood vessels.The correlation between COX-2 and angiogenesis was detected by counting the density of new blood vessels.We determine the degree of coronary artery stenosis by the application of elastic fiber staining and NIH Scion Image(60.1)software.It was comprehensively analyzed that COX-2,MMP-13 expression in atherosclerotic plaque and the correlation between them.We analyzed the correlation between these two proteins and ACS.Method: The methods of immunohistochemistry,special staining and software analysis were used in the experiment.Specimens were selected from the department of pathology and forensic medicine of Dalian Medical University in the past 5 years,totally 60 autopsy specimens.Left anterior descending branch of coronary artery,left lateral branch and right coronary artery were taken.The grouping method is three kinds.According to the different stages of atherosclerotic plaque,the tissues were divided into two groups: the fat pattern and atherosclerotic plaque group.The coronary artery tissues were divided into A group(< 25%),B group(25%-50%),C group(50%-75%)and D group(>75%)according to the degree of stenosis.According to whether there was a history of acute myocardial infarction,the cases were divided into ACS group,old myocardial infarction group and normal group.Result: The expression of ACS in COX-2 group and control group: There were differences between the three groups.The COX-2 expression of ACS group was the highest(P = 0.000,P=0.000),the old myocardial infarction group was weakest(P=0.002).The expression of COX-2 in ACS group and control group were compared with in the control group.The expression intensity of COX-2 ACS group was stronger than other two groups(old myocardial infarction group and normal group,P=0.000,0.000).There was no difference in the expression of COX-2 in old myocardial infarction group and no heart infarction group(P=0.384).The expression of COX-2 is located in the fibrous cap.The expression of COX-2 in ruptured plaques was significantly higher than non ruptured plaques(P=0.004).There were significant differences in expression of A group and other three groups(PAB=0.004,PAC=0.001,PAD=0.000).The expression of A group is the highest.There was no difference of the expression intensity of COX-2 between B group and C group(PBC=0.747),B group and D group(PBD=0.260),C group and D group(PCD=0.663).The number of local blood vessels increased with the upgrade of COX-2 expression intensity.There is a certain positive correlation between them(R=0.921,P=0.000).The expression of MMP-13 in fatty streaks group was higher than in the atherosclerotic plaque(P=0.003).Positive sites were detected in the intima of inner elastic lamina.The expression of MMP-13 in rupture was significantly higher than non rupture(P=0.002).There was significantly positive correlation between COX-2 and MMP-13 in plaque rupture location(R=0.974,P=0.000).Conclusion: 1.COX-2 participates in the occurrence and development of coronary atherosclerosis.2.COX-2 promote occurrence of acute coronary artery syndrome by inducing coronary spasm,degradation of extracellular matrix and increasing the local angiogenesis.3.There was no significant correlation between the expression of COX-2 and the degree of stenosis of atherosclerotic coronary arteries.4.The synergistic effect of COX-2 and MMP-13 promoted the rupture of atherosclerotic plaque,and induced the occurrence of ACS.