Serum tenascin-C level is associated with coronary plaque rupture in patients with acute coronary syndrome

Tenascin-C, a large oligometric glycoprotein of the extracellular matrix, increases the expression of matrix metalloproteinases that lead to plaque instability and rupture, resulting in acute coronary syndrome (ACS). We hypothesized that a high serum tenascin-C level is associated with plaque rupture in patients with ACS. Fifty-two consecutive ACS patients who underwent emergency percutaneous coronary intervention (PCI) and, as a control, 66 consecutive patients with stable angina pectoris (SAP) were enrolled in this study. Blood samples were obtained from the ascending aorta just prior to the PCI procedures. After coronary guide-wire crossing, intravascular ultrasonography (IVUS) was performed for assessment of plaque characterization. Based on the IVUS findings, ACS patients were assigned to two groups according to whether there was ruptured plaque (ruptured ACS group) or not (nonruptured ACS group). There were 23 patients in the ruptured group and 29 patients in the nonruptured group. Clinical characteristics and IVUS measurements did not differ between the two groups. Tenascin-C levels were significantly higher in the ruptured ACS group than in the SAP group, whereas there was no significant difference between the nonruptured ACS and SAP groups. Importantly, in the ruptured ACS group, tenascin-C levels were significantly higher than in the nonruptured ACS group (71.9 ± 34.9 vs 50.5 ± 20.5 ng/ml, P < 0.005). Our data demonstrate that tenascin-C level is associated with pathologic conditions in ACS, especially the presence of ruptured plaque.     

急性冠状动脉综合征患者淋巴细胞电压依赖性钾通道的变化

目的用全细胞膜片钳技术和Western印迹法,探讨急性冠状动脉综合征（ACS）患者外周血淋巴细胞电压依赖性钾通道（Kv）电流及Kv1．3蛋白表达的变化。方法收集12例ACS患者和10例健康志愿者外周血淋巴细胞,采用膜片钳全细胞电流记录方法,记录淋巴细胞膜Kv的电流密度。用Western印迹法检测外周血淋巴细胞Kv1．3蛋白的表达。结果ACS患者淋巴细胞Kv的电流密度为（2694-94）pA／pF,明显高于正常人[（1914-64）pA／pF,P〈0．01]。ACS组淋巴细胞膜电容为（2．3±40．7）pF,对照组为（2．2±0．5）pF,两组间差异无统计学意义。Western印迹结果显示ACS患者淋巴细胞Kv1．3通道表达高于正常人（P〈0．01）。结论ACS患者淋巴细胞Kv表达明显增多,说明Kv在调节ACS患者淋巴细胞的激活中起着关键性作用。     

Troponin is more useful than creatine kinase in predicting one-year mortality among acute coronary syndrome patients.

AIMS: To compare the long-term prognostic value of troponins (Tn) vs. conventional cardiac biomarker creatine kinase (CK) and CK-MB across the spectrum of acute coronary syndromes (ACS). METHODS AND RESULTS: In the prospective, observational Canadian ACS Registry, 4627 patients with ACS were enrolled from 51 centres. The CK, CK-MB, Tn samples were analysed in each hospital clinical laboratory and the results related to the reference levels of the individual laboratories. The study cohort comprised 3138 (67.8%) patients who had both CK (or CK-MB) and Tn measurements during the first 24 h of hospitalisation. Vital status at one-year was determined by standardized telephone interview. 61.2% and 59.0% of patients had abnormal Tn and CK (or CK-MB) levels, respectively. Vital status at one-year was ascertained for 2950 patients (6% lost to follow-up). Among patients with normal CK (or CK-MB) levels, elevated Tn was associated with increased one-year mortality (odds ratio [OR] 2.06; 95% CI 1.37-3.11; P=0.001). Similarly, among patients with abnormal CK (or CK-MB) levels, abnormal Tn predicted higher one-year mortality (OR 1.83; 95% CI 1.14-2.93; P=0.01). In contrast, abnormal CK (or CK-MB) was not predictive of mortality after stratification by Tn status. In multivariable analysis controlling for other known prognosticators including creatinine, abnormal Tn (adjusted OR 1.78; 95% CI 1.30-2.44; P<0.001) but not CK/CK-MB was independently associated with increased one-year mortality. CONCLUSIONS: Elevated Tn was independently associated with worse outcome at one-year, while CK or CK-MB status did not provide incremental prognostic information. Our findings support the use of Tn in the risk stratification of unselected ACS patients.     

Tenascin-C is associated with coronary plaque instability in patients with acute coronary syndromes.

BACKGROUND: Tenascin-C (TNC) is an extracellular matrix glycoprotein that increases after inflammation and injury. In cultured cells TNC has been reported to markedly induce the expression of matrix metalloproteinase-9, which stimulates collagen degradation in the fibrous cap of human atherosclerotic plaque. METHODS AND RESULTS: Immunohistochemical techniques were used to analyze the expression of TNC protein in 51 coronary atherectomy specimens obtained from patients with stable angina pectoris (SAP, n=23) or acute coronary syndromes (ACS) (n=28; unstable angina pectoris, n=20, acute myocardial infarction, n=8). Immunostaining for alpha-smooth muscle actin, CD68, CD45, and CD31 was also performed in serial sections to identify the cell types that express TNC protein. The %TNC + area (percentage of the area of immunostaining for TNC protein in the total surface area of the plaque) was larger in coronary samples with the plaque characteristics of thrombus, angiogenesis, intraplaque hemorrhage, and macrophage (CD68(+)), and lymphocyte (CD45 (+)) clusters than in coronary samples without them (52+/-3.4 vs 39+/-4.8, p<0.05; 57+/-3.7 vs 36+/-3.7, p<0.01; 51+/-3.6 vs 39+/-4.8, p<0.05; 53+/-3.4 vs 33+/-4.5, p<0.01; 56+/-4.1 vs 37+/-3.6, p<0.01, respectively). The presence of other components, such as dense fibrous tissue, neointimal hyperplasia, atheromatous gruel and calcification, was not significantly correlated with the %TNC + area. The %TNC + area was larger in coronary samples from patients with ACS than in samples from patients with SAP (56+/-3.2% vs 34+/-4.3%, p<0.01). CONCLUSIONS: The results suggest that TNC may have specific functions in coronary plaque formation and may be involved in the pathogenesis of coronary lesions in ACS.     

Decreased circulating lipoprotein-associated phospholipase A2 levels are associated with coronary plaque regression in patients with acute coronary syndrome

Objective

Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a vascular-specific inflammatory enzyme, of which increases are associated with cardiovascular events. However, the relationship between circulating Lp-PLA2 levels and coronary plaque volume has not been clarified in patients with acute coronary syndrome (ACS).

Methods

We studied 40 patients with ACS (age, 61.4 ± 8.0 years; male, 87.5%; statin use, 45.0%) who had undergone successful percutaneous coronary intervention (PCI). Plaque volume (PV) in non-culprit sites of PCI lesions was precisely determined using grayscale intravascular ultrasound (IVUS) at onset and at six months later. We then analyzed associations among PV, lipid profiles and Lp-PLA2 levels.

Results

Circulating Lp-PLA2 levels and PV significantly decreased between baseline and six months of follow-up (458.6 ± 166.7 IU/L vs. 378.4 ± 158.5 IU/L, p < 0.001 and 82.2 ± 34.8 mm³ vs. 77.3 ± 33.1 mm³, p < 0.001, respectively). The % change in PV positively and significantly correlated with % change in LDL-C and in the LDL-C/HDL-C ratio (r = 0.444, p = 0.004 and r = 0.462, p = 0.003, respectively). Furthermore, % changes in Lp-PLA2 and in PV correlated even more closely (r = 0.496, p = 0.001). The absolute change in PV also significantly correlated with the change in Lp-PLA2 levels (r = 0.404, p = 0.009).

Conclusions

Circulating Lp-PLA2 levels are associated with changes in coronary plaque determined by IVUS in patients with ACS.     

Long-term prognostic impact of the attenuated plaque in patients with acute coronary syndrome

Several intravascular ultrasound studies have reported that culprit lesion-attenuated plaque (AP) is related to slow flow/no reflow after percutaneous coronary intervention (PCI). Long-term prognostic impact of the AP is unknown. The aim of this study was to investigate acute and long-term clinical impact of the AP in patients with acute coronary syndrome (ACS). A total of 110 ACS patients who underwent successful PCI were enrolled. Acute and long-term clinical outcomes were compared between patients with AP (AP group: n = 73) and those without AP (non-AP group: n = 37). Long-term cardiac event was defined as a composite of death and ACS. Baseline characteristics in 2 groups were similar. AP was associated with higher TIMI frame count immediately after the first balloon inflation. After thrombectomy and intracoronary drug administration, final TIMI frame count became similar between AP and non-AP group. Although AP was associated with higher incidence of fatal arrhythmia during hospitalization, in-hospital mortality did not differ between the 2 groups. During follow-up (median 6.2 years), cardiac event-free survival did not differ between the 2 groups. Despite the initial unfavorable effect on coronary reflow, presence of AP did not affect acute as well as long-term clinical outcome in patients with ACS.     

急性冠状动脉综合征与稳定性冠心病斑块组织成分的比较

目的 应用血管内超声虚拟组织成像技术评价稳定性冠心病(SCAD)患者与急性冠状动脉综合征(ACS)患者冠状动脉斑块成分的差别,为探讨有效的易损斑块检测方法提供证据.方法 入选210例冠心病患者,根据临床表现分为ACS组和SCAD组.对所有直径＞2.5 mm的血管内狭窄超过50%的病变行血管内超声检查,共评价346处原位病变.应用虚拟组织学软件分析斑块成分并进行组间比较.结果 在ACS与SCAD患者间,总的冠状动脉粥样硬化斑块成分比例差异无统计学意义(纤维组织51.2%±12.5%比52.6%±9.6%,纤维脂肪组织11.3%±10.6%比12.9%±9.4%,钙化组织15.1%±8.9%比20.5%±12.5%,坏死成分23.1%±9.8%比20.4%±6.8%,均P＞0.05).两组问罪犯病变成分比例差异也无统计学意义(纤维组织49.1%±11.2%比50.3%±9.7%,纤维脂肪组织10.2%±9.5%比12.7%±9.5%,钙化组织15.4%±8.9%比17.4%±24.8%,坏死成分24.0%±11.5%比19.7%±5.3%,均P＞0.05).ACS患者中,高密度脂蛋白胆固醇＞1.04 mmol/L者与≤1.04 mmol/L者比较,斑块纤维脂肪成分较多(15.6%±9.6%比7.4%±5.9%,P＜0.05),而坏死成分较少(19.4%±8.6%比28.6%±11.2%,P＜0.05).结论 SCAD与ACS患者冠状动脉粥样硬化斑块中各种成分的比例无明显差别.因此,评价斑块的易损性不仅要看各种成分所占的比例,更重要的是关注不同成分在斑块内的空间分布以及与血管腔的关系.     

Association between abdominal fat distribution and coronary plaque instability in patients with acute coronary syndrome

Background and aimsThis study aimed to assess possible association of detailed abdominal fat profiles with coronary plaque characteristics in patients with acute coronary syndrome (ACS).Methods and resultsIn 60 patients with ACS, culprit arteries were evaluated at 1-mm intervals (length analyzed: 66 ± 28 mm) by grayscale and integrated backscatter intravascular ultrasound (IB-IVUS) before percutaneous coronary intervention. Standard IVUS indexes (as a volume index: volume/length), plaque components (as percent tissue volume) and fibrous cap thickness (FCT) were assessed by IB-IVUS. Plain abdominal computed tomography was performed to evaluate subcutaneous adipose tissue (SAT) area, visceral adipose tissue (VAT) area, and VAT/SAT ratio. While SAT area only correlated with vessel volume (r = 0.27, p = 0.04), VAT area correlated positively with vessel (r = 0.30, p = 0.02) and plaque (r = 0.33, p = 0.01) volumes and negatively with FCT (r = −0.26, p = 0.049), but not with percent plaque volume and plaque tissue components. In contrast, higher VAT/SAT ratio significantly correlated with higher percent lipid (r = 0.34, p = 0.008) and lower percent fibrous (r = −0.34, p = 0.007) volumes with a trend toward larger percent plaque volume (r = 0.19, p = 0.15), as well as thinner FCT (r = −0.53, p < 0.0001). In the multiple regression analysis, higher VAT/SAT ratio was independently associated with higher percent lipid with lower percent fibrous volumes (p = 0.03 for both) and thinner fibrous cap thickness (p = 0.0001).ConclusionCoronary plaque vulnerability, defined as increased lipid content with thinner fibrous cap thickness, appears to be more related to abnormal abdominal fat distribution, or so-called hidden obesity, compared with visceral or subcutaneous fat amount alone in patients with ACS.     

Relationships between vascular factors and plaque morphology in patients with acute coronary syndrome

Objective To investigate the relationships between vascular factors and plaque morphology in the patients with acute coronary syndrome（ACS）. Methods Intravascular ultrasound（lVUS） was performed on 56 consecutively enrolled patients with ACS. Cytometric bead array for seven vascular factors（sPE,t-PA, MCP-1, IL-8,1L-6,sVCAM-1, and sCD40L） was measured by cytometry. The others biomarkers were tested by ELISA or biochemistry. Differences in bio-factors were compared between vulnerable plaque and non- vulnerable plaque groups, accte myocardial infarction （AMI） and ustable angina （UA） patients, and occurring plaque rupture. The relationship between the parameters of morphology and vascular factors was analyzed. Results There were positive correlations between sVCAM-lsPE, sVCAM-I-sCD40L, sCD40L-sPE, IL-6-ILS,ILS-MCP1, and MCPI-sVCAM-1; CRP （18.868±4.907mg/L vs 5.806±3.553 mg/L）and IL-6 （19.5 pg/ml [9.2 - 44.6 pg/ml]vs 5.3 pg/ml [2.3- 13.4 pg/ml]）were elevated in the vulnerable plaque group（P 〈0.05）. sCD40L（473.82± 126.11 vs 237.94± 34.78 pg/ml）,sPE （107.21±39.90 vs 49.06 ±5.61ug/L） and MCP-1（132.42 ± 17.85 vs 127.17±13.27 pg/ml） were increased in the plaque rupture group（P 〈 0.05）;There was correlation between tPA and plaque morphology（P 〈 0.05）. Increases in sCD40L, MCP-1, sPE, and TC were independent factors for plaque rupture. Conclusions IL-6 and CRP may be biomarkers for vulnerable plaque and for diagnosis ofAMI, sCD40L, MCP-1 and sPE are potential markers when for plaque rupture patient present with severe ACS.     

急性冠状动脉综合征患者血管因子与冠状动脉斑块特征的相关性研究

目的探讨急性冠状动脉综合征（ACS）患者血管因子与冠状动脉斑块特征的相关性。方法选择56例ACS患者,年龄（60±11）岁,男37例,女19例,发病时取血,应用液相蛋白芯片结合流式细胞分析方法测定7种血管因子：可溶的P选择素（sPE）、组织血纤维蛋白溶酶原激活物（tPA）、单核细胞趋化蛋白1（MCP-1）、白细胞介素（IL）-8、IL-6、可溶的血管细胞间黏附分子1（sVCAM-1）和可溶的黏附分子40配体（sCD40L）,以及相应的炎症因子;常规冠状动脉造影,并用血管内超声（IVUS）检测56个靶病变处动脉粥样斑块形态学及性质特征。分析急性心肌梗死（AMI）与不稳定性心绞痛（UA）患者、易损斑块与非易损斑块组发生斑块破裂时的血管因子改变以及斑块形态学指标与血管因子的相关性。结果存在密切相关的血管因子有sVCAM-1和sPE、sVCAM-1和sCIMOL、sCD40L和sPE、IL-6和IL-8、IL-8和MCP1、以及MCP1和sVCAM-1;易损斑块组的高敏C反应蛋白（hs-CRP）为（18．9±4．9）mg／L,IL-6为[19.5ng／L（9．2—44．6ng／L）],明显高于非易损斑块组[hs-CRP：（5.8±3．6）mg／L,IL-6：5.3ng／L（2．3—13．4ng／L）,均P〈0．05];与非斑块破裂组比较,斑块破裂组的sCD40L[（474±126）ng／L比（238±35）ng／L],sPE[（107．2±39．9）ng／L比（49．1±5．6）μg／L]和MCP-1[（132±18）ng／L比（127±13）ng／L]明显升高（均P〈0．05）;tPA与斑块形态之间存在一定的相关性（均P〈0．05）。sCIMOL、MCP—1,sPE和TC水平升高是发生斑块破裂的独立危险因素（均P〈0．05）。结论炎症反应作为中间过程,IL-6和CRP标志易损斑块的生物特点,对AMI可能有一定的诊断意义,而sCIMOL、MCP-1和sPE可能是另一个潜在的反映ACS严重发作的标志。     

Toll-like receptor-4 expression in infants with pertussis infection

Purpose

Our aim was to evaluate the expression of Toll-like receptor-4 (TLR-4) and the level of interferon-gamma (IFN-γ) and interleukin-10 (IL-10) in young infants infected by Bordetella pertussis and B. parapertussis.

Methods

Twenty-two infants under the age of 3.5 months with the clinical suspicion of pertussis were enrolled in the study. Nasopharyngeal secretions were obtained for laboratory testing, and blood samples were obtained for flow cytometry and cytokine level analysis.

Results

Six infants had positive PCR results for pertussis; the other 16 infants had infections attributable to another causal agent and were used as the control group. The mean fluorescence index, used as a measure of TLR-4 expression by monocytes, was significantly lower in infants with pertussis than in the control group infants (34.32 ± 18.58 vs. 63.14 ± 28, respectively; p = 0.041). The serum IFN-γ level was also significantly lower in infants with pertussis than in the control group patients (0.41 ± 0.58 vs. 1.36 ± 1.87, respectively; p = 0.04). No differences were found in the levels of IL-10.

Conclusions

Based on these results, we suggest that TL4 expression by monocytes and serum INF-γ levels are lower in infants with positive PCR results for pertussis than in infants with a non-pertussis upper respiratory tract infection.     

光学相干断层成像对急性冠状动脉综合征患者易损斑块的新认识

血管斑块的稳定性是影响急性冠状动脉综合征发生发展的主要因素,具有超高空间分辨率的光学相干断层成像(OCT)技术在易损斑块识别方面有着独特的优势。本文就近年来OCT在急性冠状动脉综合征患者易损斑块识别方面的临床新进展进行综述。     

急性冠状动脉综合征患者易损斑块的临床病理分析

目的 观察易损斑块在急性冠状动脉综合征患者( ACS)中的病理组织学特点。方法 本研究回顾了北京医院1992-2006年尸检患者127例,分为ACS组67例;与其年龄、性别相匹配的临床表现无ACS的病例60例,从斑块的形态如有无血栓、粥池最大横切面占斑块面积、纤维帽最小厚度、炎细胞浸润密度等10个方面进行形态学观察,观...