Abstract:Aortic aneurysm (AA) is a cardiovascular disease with high morbidity and mortality. Its pathogenesis is extremely complex. Studies have confirmed that microRNA (miRNA) can regulate numerous pathophysiological processes, including inflammation, extracellular matrix (ECM) remodeling, and vascular smooth muscle cell (VSMC) proliferation and death, in AA. Matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) are important members of the MMP family, which also play an important role in the pathological process of AA. In recent years, it has been found that a variety of miRNA can directly or indirectly regulate the expression and activity of MMP-2 and MMP-9 in AA, thus affecting the occurrence and development of AA. This paper mainly summarizes the regulatory mechanisms of miRNA on MMP-2, MMP-9 and their roles in the occurrence and development of AA, so as to provide new ideas for the diagnosis and treatment of AA.

Abstract:Aim To investigate the changes of peripheral blood mean platelet volume (MPV), serum vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9) in patients with acute coronary syndrome (ACS) before and after percutaneous coronary intervention (PCI) and their correlation with prognosis. Methods The data of 96 patients with ACS in Geriatrics Hospital of Hainan were retrospectively analyzed. 15 patients with major adverse cardiovascular events (MACE) 6 months after PCI were included in the MACE group, and 81 patients without MACE were included in the non-MACE group. The levels of MPV of peripheral blood, serum VEGF and MMP-9 were compared between the two groups before and after PCI. Receiver operating characteristic curve (ROC) was used to analyze the predictive value of MPV of peripheral blood, serum VEGF and MMP-9 for MACE after PCI in ACS patients. The factors influencing prognosis of ACS patients were discussed. Results The levels of MPV of peripheral blood, serum VEGF and MMP-9 in ACS patients at 3 days and 7 days after PCI were lower than those before PCI (P＜0.05). The above indexes of MACE group before PCI, 3 days and 7 days after PCI were higher than those in non-MACE group (P＜0.05). ROC analysis showed that the area under curve (AUC) of MPV at 7 days after PCI was 0.987, which was larger than those before PCI and 3 days after PCI; When the cut-off value was greater than 11.27 fL, the sensitivity and specificity of MPV in predicting MACE in ACS patients undergoing PCI were 96.67% and 96.20% respectively. The AUC of VEGF was 0.906 at 7 days after PCI; When the cut-off value was greater than 173.80 ng/L, the sensitivity and specificity of VEGF in predicting MACE were 83.33% and 88.61% respectively. The AUC of MMP-9 was 0.843 at 7 days after PCI; When the cut-off value was greater than 334.74 μg/L, the sensitivity and specificity of MMP-9 in predicting MACE were 73.33% and 87.34% respectively. Conclusions The levels of MPV of peripheral blood, serum VEGF and MMP-9 are significantly decreased in ACS patients after PCI. MPV, VEGF and MMP-9 are important risk factors of MACE in ACS patients undergoing PCI, which have high clinical value in predicting MACE.

Abstract:Aim To investigate the intervention effect of total paeony glycoside (TPG) on matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1) and oxidative stress of vascular remodeling in spontaneously hypertensive rats (SHR). Methods 30 male 8 weeks-old SHR rats were randomly divided into 3 groups:low-dose TPG group (low-dose group, n＝10), high-dose TPG group (high-dose group, n＝10) and control group (n＝10); In addition, Wistar rats were used as a blank group (n＝8). Low-dose group and high-dose group had intragastric administration with 100 and 200 mg/(kg·d) TPG respectively, and control group and blank group had intragastric administration with 2 mL physiological saline. After 8 weeks, serum levels of MMP-9 and TIMP-1 were detected by enzyme-linked immunosorbent assay; Oxidative stress level of thoracic aorta wall cells was determined by reactive oxygen species (ROS) fluorescence probe; Expressions of MMP-9 and TIMP-1 protein in the aorta was detected by immunohistochemical staining. Results Compared with the blank group, the serum levels of MMP-9 and TIMP-1 and the expressions of MMP-9 and TIMP-1 protein in the vascular wall were significantly increased in the control group (P＜0.05). After TPG treatment, MMP-9 was decreased, and the difference between high-dose group and control group was statistically significant (P＜0.05); However, there was no significant difference in TIMP-1 among low-dose group, high-dose group and control group (P＞0.05). The ROS level of thoracic aorta in control group was significantly higher than that in blank group, while the ROS level in low-dose group and high-dose group was lower than that of the control group. Conclusion There are the increases of vascular oxidative stress and MMP-9 level in hypertensive vascular remodeling. TPG can inhibit arterial oxidative stress and MMP-9 level and improve vascular remodeling in hypertension. It can be used as an auxiliary remedy for the treatment of hypertension.

Abstract:Aim To investigate the impact of helicobacter pylori (HP) infection and cytotoxin associated protein A toxin of HP (HP-CagA) on serum matrix metalloproteinase-9 (MMP-9) in patients with coronary heart disease (CHD), and the relationship between HP-CagA and coronary lesion. Methods 105 patients with CHD were chosen in this trial, including 35 patients with acute myocardial infarction (AMI), 35 patients with unstable angina pectoris (UAP) and stable angina pectoris (SAP), while 35 inpatients with normal coronary artery (NCA) in the same period. The level of serum MMP-9, the positive rate of HP-IgG antibody and HP-CagA-IgG antibody were measured by enzyme-linked immunosorbent assay (ELISA) and the correlation between the level of serum MMP-9, the positive rate of HP-IgG antibody, the positive rate of HP-CagA-IgG antibody and coronary angiography Gensini score were analyzed respectively. The differences between CHD patients with HP infection and without HP infection were compared, and the differences between CHD patients with positive HP-CagA-IgG and negative HP-CagA-IgG were compared. Results The four groups showed significant differences in serum MMP-9 level (all P＜0.05), among them, AMI group＞UAP group＞SAP group＞NCA group (all P＜0.05). Compared to NCA group, AMI group, UAP group and SAP group were higher in Gensini score (all P＜0.05). There was significant correlation between serum MMP-9 level and Gensini score in each group (all P＜0.05). The positive rates of HP-IgG in SAP group, UA group, AMI group and NCA group were 40%, 57.1%, 74.3% and 28.6%, respectively; among them, AMI group＞UAP group＞SAP group＞NCA group (all P＜0.05); the patients with positive HP-IgG in each group showed the higher levels of MMP-9 than those with negative HP-IgG (all P＜0.05); there was significant correlation between the positive rate of serum HP-IgG and Gensini score in each group (all P＜0.05). The positive rates of HP-CagA-IgG in SAP group, UAP group, AMI group and NCA group were 17.1%, 31.4%, 40.0% and 11.4%, respectively; among them, AMI group＞UAP group＞SAP group＞NCA group (all P＜0.05); the patients with positive HP-CagA-IgG in each group showed the higher levels of MMP-9 than those with negative HP-CagA-IgG, there were statistical differences (all P＜0.05); there was significant correlation between the positive rate of serum HP-CagA-IgG and Gensini score in each group (all P＜0.05). The serum MMP-9 level among each group, HP-IgG(＋)CagA-IgG(＋) subgroup＞HP-IgG(＋)CagA-IgG(－) subgroup＞HP-IgG(－)CagA-IgG(＋) subgroup (all P＜0.05); the positive rate of serum HP-IgG and the positive rate of serum HP-CagA-IgG were significantly correlated with the serum MMP-9 level and Gensini score, especially the positive rate of serum HP-CagA-IgG was more closely related to the serum MMP-9 level and Gensini score (all P＜0.05). Conclusion HP infection especially HP-CagA infection, might be related to the occurrence and development of CHD through the large secretion of MMP-9 by endothelial cells, which might be new indicators of the severity of the coronary artery in future.

Abstract:Aim To observe the structural changes of human coronary atherosclerotic lesions and the expression of CD40L and matrix metalloproteinase-9 (MMP-9) protein, and to explore the role of CD40/CD40L signaling in the development of human coronary atherosclerosis. Methods 60 cases of human coronary artery with different degrees of atherosclerosis were collected as experimental group, and 12 cases without pathological changes were as control group. HE staining was used to observe the histological structure of coronary artery in the two groups, and image analysis software was used to detect the related indexes of the lesion structure. The expression levels of CD40L and MMP-9 protein were detected by immunohistochemical staining. The relationship between the expression of CD40L and MMP-9 and the structural changes of atherosclerotic lesions were analyzed. Results The expression of CD40L protein was enhanced in all the atherosclerotic coronary artery, and it was mainly expressed in the foam cells of the plaques shoulder and bottom. Moreover, the expression level of MMP-9 protein in the lesion was increased and it was positively correlated with the CD40L expression and the lesion size especially the necrosis size. There was no correlation between the expression level of MMP-9 and the thickness of fibrous cap. The ratio of fibrous cap thickness to the maximum intimal thickness was decreased with the increase of MMP-9 level. Conclusions The expressions of CD40L and MMP-9 protein are significantly enhanced in the human coronary atherosclerotic lesions. CD40L may promote the expression of MMP-9, to strengthen the extracellular matrix decomposition in vascular lesions, so as to promote the development of lesions and the enlargement of necrotic foci, thus the stability of atherosclerotic lesions is decreased.

Abstract:Aim To observe Helicobacter pylori (Hp) infection situation in patients with different degree of carotid atherosclerotic stenosis, and to examine the level of serum lipoprotein-associated phospholipase A2 (Lp-PLA2) and matrix metalloproteinase-9 (MMP-9); To analyze the relationship between Hp infection and carotid atherosclerosis, and to explore possible mechanism of carotid atherosclerosis caused by infection. Methods From September 2012 to September 2013 in our hospital, a total of 128 patients with carotid atherosclerosis confirmed by carotid artery ultrasound was analyzed. The carotid artery stenosis patients were divided into three groups:severe stenosis group (stenosis rate≥70% to nearly occlusion; n＝48), moderate stenosis group (stenosis rate 50%～69%; n＝45), mild stenosis group (stenosis rate＜50%; n＝35). Normal carotid artery individuals were as a control group (n＝20). Serum Hp antibody (Hp-IgG), Lp-PLA2, and MMP-9 levels were examined by enzyme-linked immunosorbent assay (ELISA). Results (1)Hp-IgG positive rate was significantly higher in patients with carotid atherosclerosis than that in the control group (64.1% vs 30.0%, P<0.05). Hp-IgG positive rate was 75.0% in severe stenosis group, 62.2% in moderate stenosis group, and 51.4% in mild stenosis group, which was significantly higher than that in control group (P<0.05). (2)The serum concentrations of Lp-PLA2 and MMP-9 in Hp-IgG positive group were significantly higher than those in Hp-IgG negative group (P<0.05). (3)The serum concentrations of Lp-PLA2 and MMP-9 in severe, moderate and mild stenosis groups were significantly higher than those in control group (P<0.05). Conclusions (1)Hp infection can increase the risk of carotid atherosclerosis. With the aggravation of Hp infection, carotid stenosis has a tendency to increase. (2)Hp infection may enhance the local inflammatory response to promote and aggravate carotid atherosclerotic stenosis through the increase of inflammatory cytokines Lp-PLA2 and MMP-9.

Abstract:Matrix metalloproteinase-9 (MMP-9), a proteinase containing Zn2+ mostly expressed in macrophages, has involved in synthesis and degradation of extracellular matrix, as well as regulation of inflammatory mediators, which facilitated the initiation and exacerbation of atherosclerosis and vascular wall remodeling, leading to the occurrence of cardiovascular events. In this review, we focused on the research progress of MMP-9 in atherosclerosis and introduced the predicting value of MMP-9 for acute myocardial infarction and cardiac remodeling of post-myocardial infarction.

Abstract:Aim To explore the effect and mechanisms of matrix metalloproteinase-9 （MMP-9）/tissue inhibitor of metalloproteinase-1 （TIMP-1） in ApoE－/－ mice kidney damage induced by hyperhomocysteinemia （HHcy）, provide theoretical and experimental basis for the prevention and treatment of kidney disease, and supply a new indicator for kidney disease surveillance. Methods 5 week old male ApoE－/－ mice were divided into three groups: ApoE－/－ control group, ApoE－/－ high methionine diet group and ApoE－/－ intervention group, and 5 week old SPF male C57BL/6J mice were chosen as normal control group. After fed for 14 weeks, the serum concentration of homocysteine （Hcy）, creatinine （Cr） and urea were detected by biochemical analyzer, transmission electron microscopy and PAS staining were used to show the damage of kidney. MMP-9 and TIMP-1 mRNA expression levels of kidney were detected by real-time PCR, MMP-9 protein expression of kidney was assayed by immunohistochemical staining and TIMP-1 protein expression was detected by ELISA. Results Compared with normal control group, the serum concentration of Hcy, Cr and urea of ApoE－/－ high methionine diet group were significantly increased by 3.66-, 1.1-and 1.6-folds （P<0.01）. Transmission electron microscopy and PAS staining showed that kidney damage of ApoE－/－ high methionine diet group were more serious than normal control group. Real-time PCR results showed that mRNA expressions of MMP-9 and TIMP-1 were evidently increased by 5.25-and 1.38-folds respectively （P<0.01）. The results of immunohistochemistry assay showed that protein expression of MMP-9 in ApoE－/－ high methionine diet group was significantly higher than that in the normal control group （P<0.01）, ELISA assay showed TIMP-1 protein expression in the ApoE－/－ high methionine diet group was significantly higher than that in the normal control group （P<0.01）. Compared with ApoE－/－ high methionine diet group, Hcy levels decreased in ApoE－/－intervention group （P<0.01）, and Cr and urea levels were significantly decreased （P<0.01）. Transmission electron microscopy and PAS staining showed that kidney damage of ApoE－/－ intervention group were relieved compared with high methionine diet group. Serum Hcy level was positively correlated with Cr and urea （r2＝0.4344, P<0.0001 r2＝0.4478, P<0.0001）, and also with the ratio of MMP-9/TIMP-1（r2＝0.39309, P<0.001）. And the ratio of MMP-9/TIMP-1 was positively correlated with Cr and urea （r2＝0.1464, P<0.05 r2＝0.3027, P<0.01）. Conclusions HHcy could cause the up-regulation of MMP-9/TIMP-1 and degradation of extracellular matrix, then lead to ApoE－/－ mice kidney damage.

Abstract:Aim To investigate the effects of atorvastatin on matrix metalloproteinase-9 （MMP-9） and tissue inhibitor of metalloproteinase-1 （TIMP-1）, and relationship between MMP-9, TIMP-1 and microalbuminuria （MAU） in essential hypertension patients with early renal damage. Methods A total of 120 essential hypertension patients with early renal damage in our hospital were selected from January 2012 to September 2013, and then were randomly divided into the observation group and the control group. The observation group was given atorvastatin 10 mg,qn and metoprolol 25～100 mg/d. The control group was given metoprolol 25～100 mg/d. After continuous treatment for 12 weeks, the folIowing indexes were detected at the beginning and end of the study: MAU, MMP-9 and TIMP-1. The microalbuminuria was calculated by urinary albumin and creatinine ratio. Results There was a significant difference in systolic pressure, diastolic pressure, MAU, MMP-9, TIMP-1, triglyceride （TG）, total cholesterol （TC）, low density lipoprotein cholesterol （LDLC） and heart rate in the observation group before and after treatment （P<0.05）. There was a significant difference in MAU, MMP-9, TIMP-1, TG, TC, LDLC between the observation group and the control group （P<0.05）. There was a significant difference in systolic pressure, diastolic pressure and heart rate in the control group before and after treatment （P<0.05）. The MMP-9 was positively related and the TIMP-1 was negatively related to the MAU in the essential hypertension. Multiple stepwise regression showed that systolic pressure, MMP-9, and TIMP-1 were three independent factors of the MAU. Conclusion The mechanism of renoprotection of atorvastatin may be related to improvement of the glomerular extracellular matrix degradation.

Abstract:Aim To investigate the correlation of matrix metalloproteinase-9 （MMP-9） levels and MMP-9-1562C＞T polymorphism with acute ischemic stroke （IS） and its “Trial of Org 10172 in Acute Stroke Treatment” （TOAST） subtypes in Uygur nationality. Methods A total of 284 patients with acute IS were enrolled using the method of case-control study, based on the standard of new TOAST classification, 91 patients were atherothrombosis （AT）, 150 patients were small artery disease （SAD） and 43 patients were cardioembolism （CE）. Meanwhiie, 226 age-and sex-matched physically healthy subjects were used as control group. The levels of serum MMP-9 and-1562C＞T gene polymorphism in each group were measured and analyzed by enzyme-linked immunosorbent assay and restriction fragment length polymorphism. Results The serum MMP-9 level in the IS group was sigrfificantly higher than that in the control group （0.308±0.033 mg/L vs 0.087±0.011 mg/L, t＝7.813, P＝0.000）. The serum MMP-9 level in the AT group and CE group were significantly higher than those in the groups of SAD （0.350±0.030 mg/L vs 0.261±0.029 mg/L, t＝4.156, P＝0.001 0.317±0.043 mg/L vs 0.261±0.029 mg/L, t＝2.877, P＝0.031）. Multivariate Logistic regression analysis showed that the increased serum MMP-9 level was an independent risk factor for ischemic stroke （OR: 1.012, 95% CI: 1.007～1.016, P<0.001）. There was no significant difference in the frequencies of genotype （χ2＝3.558, P＝0.058） and allele （χ2＝3.567, P＝0.059） of MMP-9-1562C＞T between the IS group and the control group. However, there were significant difference in the frequencies of genotype （χ2＝5.097, P＝0.024） and allele （χ2＝5.439, P＝0.02） of MMP-9-1562C＞T between the AT group and the control group. The CT＋TT genotype frequency in the AT group was significantly higher than the control group （24.2% vs 13.7%）. Multivariate Logistic regression analysis showed that MMP-9-1562C＞T polymomhism was not an independent risk factor for the IS group （OR: 0.821, 95% CI: 0.622～1.059, P＝0.124）, but it was an independent risk factor for the AT group （OR: 1.768, 95% CI: 1.178～2.677, P＝0.007）. Conclusions The serum MMP-9 level increased in Uygur patients with IS, especially in the patients with AT.