Vulnerable Plaque Group Research Articles

Correlations of MMP-1, MMP-3, and MMP-12 with the degree of atherosclerosis, plaque stability and cardiovascular and cerebrovascular events.

We analyzed the effects of matrix metalloproteinase (MMP)-1, MMP-3, and MMP-12 on the degree of carotid atherosclerosis (CAS) and plaque stability, and investigated their correlations with cardiovascular and cerebrovascular events (CCEs). Two hundred CAS patients were enrolled. Carotid intima-media thickness (IMT) was measured using ultrasonic examination. Patients were divided into the no plaque group (NP group), stable plaque group (SP group), and vulnerable plaque group (VP group). The Crouse method was used for the evaluation of plaque scores. Additionally, 60 healthy subjects were enrolled as the control group. Serum triacylglycerol (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), and high density lipoprotein cholesterol (HDL-C) were analyzed. The serum protein levels of MMP-1, MMP-3, and MMP-12 were measured by western blotting. The frequency of CCEs within 2 years was recorded, and its correlation with MMP-1, MMP-3, and MMP-12 was analyzed. The CAS plaque scores in the SP and VP groups were significantly increased compared with the NP group, and the difference between the SP and VP groups was significant. The levels of TC, TG, LDL-C, and HDL-C of CAS patients were significantly increased compared with those in the control group, but the differences in these indexes between the patient groups were not significant. Western blotting showed that the levels of MMP-1, MMP-3, and MMP-12 in the patient groups were significantly increased compared with those in the control group, and the protein levels in the VP group were significantly higher than those in the SP and NP groups. Additionally, the levels of MMP-1, MMP-3, and MMP-12 had significantly positive correlations with the occurrence of CCEs in CAS patients. In conclusion, MMP-1, MMP-3, and MMP-12 are positively correlated with CCEs in CAS patients. They can be used as markers for the clinical diagnosis and prognosis of CAS.

Serum lipoprotein-associated phospholipase A2 predicts the formation of carotid artery plaque and its vulnerability in anterior circulation cerebral infarction

ObjectiveCirculation inflammation markers such as high-sensitive C-reactive protein (hsCRP) and lipoprotein-associated phospholipase A2 (Lp-PLA2) are considered as predictors of cerebral and cardiac vascular diseases. However, the role of hsCRP and Lp-PLA2 in the anterior circulation cerebral infarction (ACI) is to be elaborated. Patients and methodsWe included 100 patients with acute anterior circulation cerebral infarction (AaCI group) and 50 non-infarction subjects (control group). Carotid artery was detected by color Doppler ultrasound. Subjects were grouped based on carotid intima-media thickness (IMT) and degree of stability of carotid atherosclerotic plaque. The levels of hsCRP and Lp-PLA2 were measured in corresponding groups and the association was analyzed. ResultshsCRP and Lp-PLA2 levels were the risk factors for AaCI. With the increment of carotid IMT and degree of plaque instability, the level of hsCRP and Lp-PLA2 showed an elevating tendency. hsCRP and Lp-PLA2 levels were significantly higher in plaque formation group than in IMT normal group (P=0.002 and P=0.001, respectively). hsCRP and Lp-PLA2 levels were significantly higher in vulnerable plaque group than in mixed plaque group and stable plaque group (P=0.003, P<0.001 for hsCRP and P<0.001, P<0.001 for Lp-PLA2). Lp-PLA2 was finally included in the atherosclerotic plaque model (OR=1.019, 95% confidence interval (CI): 1.003–1.035, P=0.020) and vulnerable plaque model (OR=1.041, 95%CI: 1.017–1.065, P=0.001) by performing multivariate logistic regression analysis. The area under the ROC curve (AUC) of Lp-PLA2 levels for atherosclerotic plaque was 0.746 (95% CI: 0.628–0.865, P<0.001). The optimal cut-off value for Lp-PLA2 level was 267.5ng/ml, and its sensitivity and specificity for diagnosis of atherosclerotic plaque were 70.8% and 67.1%, respectively. ConclusionsThe current study demonstrates that hsCRP and Lp-PLA2 are among the risk factors for AaCI. Elevated hsCRP and Lp-PLA2 are associated with carotid plaque formation. Univariate and multivariate logistic regression analysis suggests that elevated Lp-PLA2 is the independent risk factor for carotid plaque and its vulnerability.

Alpha-2-macroglobulin and heparin cofactor II and the vulnerability of carotid atherosclerotic plaques: An iTRAQ-based analysis

Rupture of carotid atherosclerotic plaque may cause stroke, while few biomarker in clinic can evaluate carotid plaque vulnerability. In this study, we divided the recruited participants into no plaque, stable plaque, and vulnerable plaque group according to carotid ultrasonography, and screened the differentially expressed proteins in plasma of these participants using isobaric tags for relative and absolute quantitation labeling coupled with liquid chromatography-tandem mass spectrometry. 28 proteins were identified differentially expressed, among which alpha-2-macroglobulin (α2M) and heparin cofactor II (HCII) were found to be at hub position in the interactions of these proteins by STRING analysis and were selected for enzyme-linked immunosorbent assay measurement to assess their relevance with carotid plaques vulnerability and diagnostic efficiency. The plasma level of α2M was found positively correlated, while HCII level was negatively correlated with higher vulnerability of carotid plaques. Both proteins were efficient in differentiating stable and vulnerable carotid plaques. These findings provide potential new targets for the research of carotid plaque vulnerability. Plasma α2M and HCII may be potential biomarkers for evaluation of the vulnerability of carotid plaques if further studied.

Low serum miR-320b expression as a novel indicator of carotid atherosclerosis

We aimed to investigate correlation of carotid plaque with serum microRNA level and provide a potential mechanism for ischemic stroke prevention. Fasting serum was obtained from 177 patients with carotid plaques diagnosed using B ultrasound and 155 healthy subjects for RNA extraction and measurement of glucose, lipid and related biochemical indices. microRNAs level was assayed using microarray, validated using real-time PCR and statistically analyzed for their correlation with relevant clinical information. Statistical analyses showed significant differences between control and plaque groups in age, smoking history, and histories of cerebrovascular diseases, blood pressure, diabetes and coronary diseases. Patients in plaque group had significantly higher LDL-C level but significantly lower miR-320b level than healthy subjects. The P50 (P25–P75) of miR-320b was 2.38 (1.46–3.80) in control group and 1.20 (0.80–2.01) in plaque group (P=0.000), as well as 1.39 (0.83–2.08) in stable plaque group and 0.77 (0.590.99) in vulnerable plaque group (P=0.000). The area under the ROC curve of traditional factors, miR320b with traditional factors, traditional factors with plaque diameter, and traditional factors with IMT for patients with carotid plaques was 0.710, 0.834, 0.826 and 0.808, respectively. This study suggests that miR-320b is a specific serum marker of carotid atherosclerosis and vulnerable plaque, and its combination with traditional factors is the best means for diagnosis of cerebrovascular diseases. The carotid atherosclerosis complicated with vulnerable plaque is a high risk factor for cerebral infarction. B-ultrasound examination combined with serum miR-320b expression and traditional indices could be used to predict subjects with high-risk for ischemic stroke.

Mesenchymal Stem Cells Stabilize Atherosclerotic Vulnerable Plaque by Anti-Inflammatory Properties.

Background and objectivesFormation and progression of atherosclerotic vulnerable plaque (VP) is the primary cause of many cardio-cerebrovascular diseases such as acute coronary syndrome and stroke. It has been reported that bone marrow mesenchymal stem cells (MSC) exhibit protective effects against many kinds of diseases including myocardial infarction. Here, we examined the effects of intravenous MSC infusion on a VP model and provide novel evidence of its influence as a therapy in this animal disease model.Subjects and methodsThirty healthy male New Zealand white rabbits were randomly divided into a MSC, VP or stable plaque (SP) group (n = 10/group) and received high fat diet and cold-induced common carotid artery intimal injury with liquid nitrogen to form atherosclerotic plaques. Serum hs-CRP, TNF-α, IL-6 and IL-10 levels were measured by ELISA at 1, 2, 3, 7, 14, 21 and 28 days after MSC transplantation. The animals were sacrificed at 4 weeks after MSC transplantation. Lesions in the right common carotid were observed using H&E and Masson staining, and the fibrous cap/lipid core ratio of atherosclerotic plaques were calculated. The expression of nuclear factor κB (NF-κB) and matrix metalloproteinase 1, 2, 9 (MMP-1,2,9) in the plaque were detected using immunohistochemistry, and apoptotic cells in the plaques were detected by TUNEL. In addition, the level of TNF-α stimulated gene/protein 6 (TSG-6) mRNA and protein were measured by quantitative Real-Time PCR and Western blotting, respectively.ResultsTwo rabbits in the VP group died of lung infection and cerebral infarction respectively at 1 week after plaque injury by liquid nitrogen. Both H&E and Masson staining revealed that the plaques from the SP and MSC groups had more stable morphological structure and a larger fibrous cap/lipid core ratio than the VP group. Serum hs-CRP, TNF-α and IL-6 were significantly down-regulated, whereas IL-10 was significantly up-regulated in the MSC group compared with the VP group. .Immunohistochemistry analysis revealed that NF-κB and MMP expression was reduced in the MSC and SP groups compared to the VP group. Cell apoptosis decreased significantly in both the MSC and SP groups in comparison to the VP group. TSG-6 mRNA and protein expression were higher in the plaques of the MSC group compared to the VP and SP groups.ConclusionsOur study results suggest that MSC transplantation can effectively stabilize vulnerable plaques in atherosclerotic rabbits. This may potentially offer a new clinical application of MSC in atherosclerosis.

The expression of CD40 and matrix metalloproteinase in canotid endarterectomy plaques and the study of plaque stability

Objective To study the expression level of CD40 and matrix metalloproteinase (MMPs) in vulnerability, stability carotid atherosclerotic plaque. Investigate the relevance of CD40 and MMPs expression and the impact on plaque stability. Methods Thirty-two cases of specimens with carotid atherosclerotic plaque were collected from carotid endarterectomy(CEA). According to preoperative carotid ultrasound, transcranial doppler (TCD) and the presence of acute ischemic stroke events, all specimens were divided into stable plaque group and vulnerable plaque group, detected the mRNA and protein expression level of CD40 and MMPs in each group using PCR and western blotting assay. Results The mRNA and protein expression level of CD40 and MMP-9 in vulnerable plaque group was significantly higher than in stable plaque group respectively(P<0.01). The MMP-2 protein expression level in vulnerable plaque group was distinctly higher than in stable plaque group(P<0.01). There were positive correlation between CD40 mRNA and MMP-2 mRNA (r=0.43, P<0.05), CD40 mRNA and MMP-9 mRNA (r=0.90, P<0.01) respectively. Conclusion CD40 is not only involved in the formation of atherosclerotic plaque, but also may influence the stability of atherosclerotic plaques by regulating the expression of MMP-2 and MMP-9. Key words: Carotid endarterectomy; Atherosclerosis; Plaque stability; Antigens, CD40; Matrix metalloproteinases

Positive association of MMP 14 gene polymorphism with vulnerable carotid plaque formation in a Han Chinese population

Background. MMP 14 is expressed in atherosclerotic plaques and potentially plays an important role in the development of vulnerable carotid plaques. MMP 14 gene polymorphisms can influence the bioactivity or expression of MMP 14. Objective. The aim of this study was to investigate the association between MMP 14 position + 7096 T > C (NM_004995.2:c.855T> C, rs2236307) polymorphism and vulnerable carotid plaque formation. Methods. 1370 patients with ischemic cerebral infarctions were enrolled and divided into three groups according to their carotid ultrasound examination: No plaque group (n = 346), stable plaque group (n = 695) and vulnerable plaque group (n = 329). The traditional atherosclerosis risk factors were recorded, and the MMP 14 polymorphism were genotyped by Applied Biosystems 7300 Real-Time PCR System using the TaqMan assay. Results. In the multiple logistic regression analysis done among the sub-groups, compared to no carotid plaque group, individuals with the MMP 14 position + 7096 TC+ CC genotype showed a significantly (p = 0.009) lower risk for vulnerable plaque (AOR = 0.675; 95% CI, 0.568–0.922) formation compared with subjects of the TT genotype; however, no relation between TC+ CC genotype and stable carotid plaque was observed (p > 0.125). Age was a risk factor for both stable plaque (p = 0.000; AOR = 3.732; 95% CI: 2.496–5.58) and vulnerable plaque formation (p = 0.001; AOR = 2.234; 95% CI: 1.387–3.597). Meanwhile, fibrinogen (> 4.0 g/L) was a risk factor for stable plaque (p = 0.004; AOR = 2.313; 95% CI: 1.308–4.091). Conclusions. The MMP 14 position + 7096 TC+ CC genotype might lower the risk of vulnerable carotid plaque formation. Fibrinogen (> 4.0 g/L) was a risk factor for stable plaque.

Intravenous infusion of mesenchymal stem cells can stabilize vulnerable atherosclerotic plaque

Objective To establish the vulnerable atherosclerotic plaque model with rabbits and treat them with intravenous infusion of bone marrow mesenchymal stem cells(MSCs),so as to verify the impact of MSCs on the stability of vulnerable plaque(VP).MethodsTotally 24 healthy male New Zealand white rabbits were randomly divided into three groups.Carotid vulnerable atherosclerotic plaque models were made with rabbits in VP group(n=8) and VP+MSCs group(n=8);VP+MSCs group was given intravenous infusion of 1×107 MSCs immediately after modeling and VP group was infused with phosphate buffer.Stable atherosclerosis plaque model was made with rabbit in SP group(n=8).Animals in all groups were sacrificed at the end of the 12th week,and the right common carotid arteries were collected and subjected to H-E staining and Masson staining,and the cap/core ratio of atherosclerotic plaque was measured.MMP-2 content was examined by immunohistochemistry.ResultsH-E staining.In VP group the plaque showed a large lipid core and thin fibrous cap,remnants of foam cells and many inflammatory cells were seen in the plaque shoulder,and some showed rupture plaques and/or thrombosis.In SP group,the structure of plaque was in integrity,with thick fibrous cap and fewer inflammatory cells,and with no plaque rupture.The plaque structure of VP+MSCs group was between those of the other two groups.The order of cap/core ratio was SP group VP+MSCs group VP group,with that of VP group being significantly different from those of the other two groups(P0.01).Masson staining.The contents of muscle fiber and elastic fiber were the highest in SP group,followed by VP+MSCs group,and then by VP group.The level of MMP-2 in VP group was significantly higher than those in the other two groups(P0.01),and that in VP+MSCs group was significantly higher than that in SP group(P0.01).ConclusionIntravenous infusion of MSCs can improve the stability of plaques in VP rabbit model,which may be associated with the reduction of inflammatory cells and MMP-2 level,and the subsequent reduction of collagen fiber degradation.

Association between matrix metalloproteinase-10 gene polymorphisms and instability of carotid plaque

To assess the association between 2 single nucleotide polymorphisms (SNPs) located in exonic regions of matrix metalloproteinase-10 (MMP-10) gene and instability of carotid plaques in a Han Chinese population. Five hundred and eighty-five patients were divided into carotid vulnerable plaque group (n=206) and stable plaque group (n=379) based on results of carotid B-mode ultrasonography. The SNPs were genotyped by real-time polymerase chain reaction using an ABI 7300 TaqMan platform. The distribution of rs17435959 between the two groups was significantly different at both genotypic (GC+CC vs. GG, P=0.006, OR=2.012) and allelic levels (C vs. G, P=0.001,OR=2.160). Above differences have remained significant with binary logistic regression analysis (P=0.007, OR=2.022; P=0.002, OR=2.104). The minor allele frequency of rs17293607 was 0.56%. Above findings suggested that rs17435959 of the MMP-10 gene is associated with carotid vulnerable plaque in ethnic Chinese Hans. The C allele may be a susceptible predictor for carotid vulnerable plaque.

Plaque Image Characteristics, Hyperhomocysteinemia, and Gene Polymorphism of Homocysteine Metabolism-Related Enzyme (MTHFR C677T) in Acute Coronary Syndrome

This study aims to investigate the correlation between the different characteristics of plaques, plasma level of homocysteine (Hcy), and gene polymorphism of Hcy metabolism-related enzyme. In this consecutive case-control study, we measured the plasma Hcy level using fluorescence biochemistry method and examined the gene polymorphism of Hcy metabolism-related enzyme methylenetetrahydrofolate reductase (MTHFR) C677T using TaqMan probe technology. We also examined these using intravascular ultrasound. We studied the characteristics of the plaque, measured the cross-sectional areas of the external elastic membrane and the lumen, calculated the plaque area, plaque burden, and eccentricity index, and examined the remodeling index. Hard plaques were more dominant in the (SPA) group, whereas soft plaques were more dominant in the acute coronary syndrome (ACS) group (P < 0.001). The risk of plaque rupture and thrombus is higher in the ACS group (P < 0.05). Compared with SPA group, plaque burden was heavier in the ACS group (P < 0.05), but the eccentricity index is significantly higher in SPA group than in the ACS group (P < 0.001). Positive remodeling was more frequent in ACS group, whereas negative remodeling was more frequent in the SPA group (P < 0.001). Plasma Hcy levels were higher in the unstable than in the stable plaque group (P < 0.001). The constituent ratio of MTHFR C677T genotype were different in stable plaque group and vulnerable plaque group (P < 0.05). The T genotype can increase the incidence rate of vulnerable plaque. Hcy and MTHFR C677T gene polymorphism were found to be risk factors for vulnerable plaque. Therefore, these can be used as indices to predict the instability of atherosclerotic plaque.

Lack of independent relationship between the MMP-12 gene polymorphism and carotid plaque susceptibility in the Chinese Han population

The purpose of this study was to investigate whether a polymorphism in the matrix metalloproteinase-12 gene (MMP-12 -82A/G) is correlated with serum protein levels or with the susceptibility for carotid plaques in the Chinese Han population. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed on the -82A/G polymorphism in the MMP-12 gene for 1314 patients with acute cerebral infarctions; 710 of these cases were diagnosed with stable plaques, 340 cases were diagnosed with vulnerable plaques and 264 cases had no plaques. At the same time, serum MMP-12 levels were measured using the enzyme-linked immunosorbent assay (ELISA). Compared to the AA genotype, the frequency of the AG+GG genotypes was not significantly different between the three groups (χ(2) = 1.242, p = 0.537), and the frequency of the G allele of the MMP-12 gene was not different within the three subgroups (χ(2) = 1.218, p = 0.544). There were no significant differences in MMP-12 protein levels among the three groups (F = 0.675, p = 0.510); similarly, there was no difference in MMP-12 protein levels between the stable plaque group and the vulnerable plaque group (p = 0.755). There was also no difference between the vulnerable plaque group and the no plaque group (p = 0.420). The current data suggest that the inter-individual variability in the MMP-12 gene variation may not be a risk factor for vulnerable plaques in the Chinese Han population.

Association between matrix metalloproteinase-8 -799C/T polymorphism and instability of carotid plaque

To investigate the association between a -799C/T polymorphism in the promotor region of matrix metalloproteinase-8 (MMP-8) gene and instability of carotid plaque in Chinese Han population. A total of 451 acute infarction patients from the Department of Neurology of Taizhou Hospital were divided into carotid vulnerable plaque group and carotid stable plaque group according to the results of carotid B-mode ultrasonography. Serum MMP -8 level was measured by the means of enzyme-linked immunosorbent assay (ELISA). At the same time, the MMP-8 -799C/T polymorphism was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Serum level of MMP-8 in the carotid vulnerable plaque group was higher than that in the carotid stable plaque group (t= 2.894, P= 0.004). The genotype distribution of -799C/T polymorphism between the two groups was significantly different (Chi-square = 13.65, P= 0.000). Serum level of MMP-8 in patients with TT genotype was higher than that in patients with CC genotype (t= 3.141, P= 0.001). The present study suggested that serum level of MMP-8 and the -799C/T polymorphism of MMP-8 gene are associated with carotid vulnerable plaque in Chinese Han population, and the T allele may be a predictor for the susceptibility of carotid vulnerable plaque.

Abstract 18045: Can Metabolic Syndrome Predict the Vulnerable Plaque in Patients with Stable Angina Pectoris?: Virtual Histology-Intravascular Ultrasound Analysis

Background- Vulnerable plaque (VP) in coronary artery can progress to plaque rupture and thrombosis, and have a strong potential to induce acute coronary syndrome. Many studies have demonstrated that metabolic syndrome (MS) is associated with increased risk for cardiovascular diseases and related mortalities. This study aimed to determine the predictive value of MS on VP in the patients with stable angina pectoris (SAP). Methods and Results- From September 2007 to June 2010, a total of 239 patients with SAP who underwent coronary angiogram and intravascular ultrasound were categorized into two groups: MS group (n = 100, 56 men, 64.7 ± 9.5 years) and non-MS group (n = 139, 98 men, 60.2 ± 8.4 years). National Cholesterol Education Program-Adult Treatment Panel III guideline was used to determine the presence of MS and diverse variables containing IVUS findings were compared between two groups. MS group were older age and more likely to be women than non-MS group (p &lt;0.001, p = 0.021, respectively). MS group showed more frequent multivessel involvement (p = 0.026) and had more distal target vessel in coronary artery (p = 0.005) than non-MS group, but IVUS finding containing the plaque burden showed no significant difference between two groups. In addition, low high density lipoprotein (HDL) cholesterol level as the criteria of MS (male &lt;40 mg/dl, female &lt;50 mg/dl) was observed in VP group more than stable plaque group (p = 0.020), but the prevalence of MS and other components of MS were not different between two groups. Multivariate analysis using logistic regression for the presence of VP showed that the independent predictor is the low HDL cholesterol level (odds ratio = 3.563, 95% confidence interval = 1.370-9.269, p = 0.009). Conclusions- Low HDL cholesterol level, but not MS, is the independent predictor of VP as a culprit lesion in SAP patients.

Relations between plasma Ox-LDL and carotid plaque among Chinese Han ethnic group

<title/>Objectives: To study the relationship between plasma oxidized low-density lipoprotein (ox-LDL) and carotid plaque, including plaque stability, of patients with acute ischemic stroke among Chinese Han ethnic group.Methods: A total of 181 patients with acute ischemic stroke were recruited and enrolled. The subjects were divided into a carotid plaque group and a no-plaque group by carotid ultrasound. The stability of carotid atheromas was assessed by ultrasound echo density, and the carotid plaque group was further divided into a vulnerable plaque group and a stable plaque group based on the echo results.Results: The study showed that the correlation between age [odds ratio (OR): 1·047; 95% confidence interval (CI): 1·014-1·082; P<0·01] and carotid plaque was significant. Plasma ox-LDL (OR: 1·020; 95%CI: 1·010-1·030; P<0·001) was also found to be significantly correlated with carotid plaque. Age was irrelevant to plaque stability (P = 0·0685). The ox-LDL of the vulnerable plaque group was found to be significantly higher than that of the stable plaque group (P = 0·015). By measuring the plasma ox-LDL in patients with ischemic stroke, the proportion under the receiver operating characteristic curve of vulnerable carotid plaques was 0·690 with a 95%CI of 0·613-0·767 (P<0·001). The point of cut-off was 94·5943, the sensitivity was 0·805, and the specificity was 0·505.Conclusion: The plasma ox-LDL level and age are possible risk factors for carotid plaque among patients with ischemic stroke of the Chinese Han ethnic group. This study suggests that ox-LDL could be used as a biomarker in screening for vulnerable carotid plaque in clinical practice.

Association of a functional polymorphism in the MMP7 gene promoter with susceptibility to vulnerable carotid plaque in a Han Chinese Population

Matrix metalloproteinase-7 (MMP-7) may play an important role in the development of vulnerable carotid plaque. An A-to-G transition (-181A/G) in the promoter region of MMP7 is functional in vitro by altering the transcriptional activity of the gene. The aim of this study was to investigate the association between the MMP7 -181A/G polymorphism and vulnerable carotid plaque formation. The authors enrolled 641 patients and divided them into three groups according to the carotid ultrasound examination: vulnerable plaque group (n=118), stable plaque group (n=385) and no plaque group (n=138). Traditional atherosclerosis risk factors were recorded and the MMP7 -181A/G polymorphism was genotyped by polymerase chain reaction-restriction fragment length polymorphism. In the multinomial logistic regression analysis, compared to the no plaque group, no relationship between MMP7 -181AG+GG genotypes and stable carotid plaque was observed [odds ratio (OR) 1.50; p=0.239]. However, the frequency of AG+GG genotypes was significantly higher in the vulnerable plaque group (OR 2.74; p=0.008). Age was a risk factor for plaque formation, while statin treatment can reduce the prevalence of atherosclerotic plaque. Additionally, using binary logistic regression analysis between the stable and vulnerable plaque groups, this MMP7 polymorphism was associated with vulnerable plaque independently of other factors [OR 1.83; 95% confidence interval 1.08- 3.11; p=0.026]. The MMP7 -181A/G polymorphism is associated with the development of vulnerable carotid plaques. Age is a risk factor for plaque formation, while statin therapy is associated with a decreased prevalence of carotid atheromatous plaques.

Association of the ALOX5AP gene SG13S114 A/T polymorphism with atherosclerosis

To investigate the relationship between the polymorphism of SG13S114 A/T in the 5-lipoxygenase-activating protein (ALOX5AP) gene and the stability of carotid atherosclerosis. Polymorphism of SG13S114 A/T in the ALOX5AP gene was analyzed in 152 cases of acute infarction with stable plaque, and 132 cases of acute infarction with vulnerable plaques, by using polymerase chain reaction and restriction fragment length polymorphism. Carotid artery plaque was analyzed by carotid artery color ultrasound. The frequencies of SG13S114 AA genotype and the A allele in the vulnerable plaque group were higher than that in the stable plaque group (P< 0.01). The polymorphism of SG13S114 A/T in the ALOX5AP gene may be associated with the instability of atherosclerosis. And the SG13S114 A allele may be a risk factor of vulnerable plaques.

Relationship between lectin-like oxidized low-density lipoprotein receptor 1 expression and preoperative echogenic findings of vulnerable carotid plaque

Lectin-like oxidized low-density lipoprotein 1 (LOX1) is an important cell surface receptor for the progression of atherosclerosis. Our purpose is to clarify the relationships of LOX1 and atherosclerotic factors for the vulnerability of carotid plaque and preoperative echogenic findings. We examined LOX1 expression, matrix metalloproteinase (MMP)-2,9, and tissue inhibitor of MMP (TIMP)-2 by immunohistochemical analysis using carotid endarterectomy specimens obtained from 14 patients. Groups were divided into stable plaque group A and vulnerable plaque group B by preoperative echogenic findings of carotid plaques. Endothelial immunoreactivity was calculated, and the immunohistochemical findings were compared. LOX1 was remarkably expressed, especially in smooth muscle cells in vulnerable plaque and colocalized in MMP-9 positive cells and apoptotic cells. All LOX1, MMP-2,9, and TIMP2 were remarkably expressed in the subendothelial layer in group B compared with group A. The endothelial LOX1 index was 63.75 +/- 4.92 in group A and 83.0 +/- 5.02 in group B (p = 0.02). The endothelial MMP-2 index was 24.38 +/- 5.50 in group A and 32.83 +/- 6.79 in group B (p = 0.01). The endothelial MMP-9 index was 46.13 +/- 6.31 in group A and 59.17 +/- 2.14 in group B (p = 0.002). The endothelial TIMP-2 index had no significant difference between two groups (p = 0.14). LOX-1 may play an important role in the progression of vulnerable carotid plaque and might regulate vulnerable plaque formation in cooperation with MMPs and TIMP-2. Endothelial MMP-2 might suppress TIMP-2 activation in vulnerable plaques.

Relationship between intravascular ultrasound imaging features and soluble serum CD105 level in patients with different coronary lesions

Objective To assess the relationship between the level of serum soluble CD105 and the morphology of plaques examined by intravaseular ultrasound (IVUS) in the patients with stable angina (SA) and unstable angina (UA). Methods 127 patients suspected as having coronary heart disease (CHD) underwent coronary artery angiography (CAG) and then divided into 3 groups according to the CAG results:stable angina (SA) group (n =50), unstable angina (UA) group (n =47), and control group (n =30).Peripheral blood samples were collected and serum soluble CD105 was measured by ELISA. 31 patients from the SA group and 31patients from the UA group underwent IVUS. Results The patients of the SA group mainly had fibrous plaques, while the patients of the UA group mainly had unstable and soft lipid plaques.Calcific plaques were found in the SA group ( 12% ) as well as in the UA group with no statistical difference (18.0%, P=0.08). The eccentric index (EI) of the UA group was 0.82±0.55, significantly higher than that of the SA group (0.54±0.23, P＜0.05 ). The serum soluble CD105 level of the UA group was (4.06±0.19 ) μg/L, significantly higher than that of the control group and SA group [ ( 2.57±0. 54)μg/L and (3.47±0.17) μg/L respectively, both P＜0.05 ], and serum soluble CD105 level of the SA group was significantly higher than that of the control group too ( P＜0.05). The concentration of soluble CD105 in vulnerable plaque group was (4.01±0.18 )μg/L, significantly higher than that of the stable plaque group [ (3.22±0.16 ) μg/L, P＜0.01 ]. Conclusion The serum soluble CD105 level of the UA group is significantly higher than those of the patients with SA and those without CHD. The level of soluble CD105may reflect the instability of CHD as well as the vulnerability of plaques. Key words: Angina pectoris ; Vitrasonography, interventional; Soulable CD105