蛋白芯片法联检急性冠状动脉综合征患者血中细胞因子的意义

目的 探讨急性冠状动脉综合征(ACS)患者血中炎性细胞因子、炎性细胞相关因子及心肌损伤因子浓度的变化及临床意义.方法 运用蛋白芯片技术同步联检经冠状动脉造影及临床表现证实为ACS患者104例及对照者50例血清或血浆中10种细胞因子水平;同时对不稳定性心绞痛(UA)患者按Braunwald分级进行分析.结果 急性心肌梗死(AMI)组和UA组血清中C反应蛋白(CRP)、白介素(IL)-6、可溶性CD40L(sCD40L)、基质金属蛋白酶(MMP)-9、心脏型脂肪酸结合蛋白(H-FABP)、肌钙蛋白Ⅰ(cTnⅠ)及血浆中的IL-8、内皮素(ET)-1、可溶性血管细胞黏附分子(sVCAM)-1、氨基酸N末端脑钠肽原(NT-proBNP)浓度高于对照组,差异有统计学意义(P＜0.01);AMI组cTnⅠ[(11.08±10.49) μg/L]和H-FABP[(19.80±4.60)μg/L]浓度高于UA组[cTnⅠ:(0.69±0.18)μg/L,H-FABP:(4.12±2.45)μg/L,P＜0.01],而CRP、IL-6、MMP-9、sCD40L及ET-1浓度,两组比较差异无统计学意义;UA组MMP-9、sCD40L及H-FABP的浓度与Braunwald分级存在显著正相关(分别r=0.653,r=0.745,r=0.933,均P＜0.01).随着心绞痛严重程度的增加,MMP-9、sCD40L及H-FABP水平明显升高,心绞痛Ⅰ级＜心绞痛Ⅱ级＜心绞痛Ⅲ级(P＜0.01).结论 ACS患者血中存在多种细胞因子浓度异常,其中MMP-9、sCD40L、H-FASP的浓度与UA患者心绞痛严重程度存在良好的相关性.提示上述细胞因子参与和促使了ACS的发生、发展,为ACS的危险分层、预后判断提供了可能的分子标志物依据.     

经皮冠状动脉介入术联合经皮血栓吸除术治疗急性心肌梗死的临床评价

目的 评价经皮冠状动脉介入术(PCI)联合经皮血栓吸除术治疗急性心肌梗死(AMI)的疗效.方法 56例AMI患者随机分为PCI组(n=28)和PCI联合血栓吸除术组(n=28).于PCI术后24小时、1周行实时心肌声学造影(RT-MCE),记录各组灌注对比积分指数(CSI)、室壁运动积分指数(WMSI)、透壁性对比缺损长度(CDL)和严重室壁运动异常长度(WML).采用免疫散射比浊法测定血浆超敏C-反应蛋白(hs-CRP)水平,酶联免疫吸附法测定血浆N-末端脑利钠肽(NT-ProBNP)和基质金属蛋白酶-9(MMP-9)水平.结果 各时间点PCI联合血栓吸除术组CSI、WMSI、CDL和WML明显低于PCI组(P＜0.05).术后1周PCI联合血栓吸除术组血浆hs-CPR和NT-ProBNP水平低于对照组[(4.56±1.98)mg/L比(5.96±2.03)mg/L,P＜0.05;(544.7±185.3)pmol/L比(897.6±215.9)pmol/L,P＜0.01],血浆MMP-9无明显升高[(672.7±175.9)μg/L比(609.6±196.5)μg/L,P＞0.05].结论 与PCI组相比,PCI联合经皮血栓吸除术可明显减少术后无再流的发生,改善微循环和心脏功能,是治疗AMI的有效方法.     

芪参益气滴丸对冠状动脉介入术后炎症因子及心脏不良事件的影响

目的 观察芪参益气滴丸对急性冠脉综合征（ACS）患者经皮冠状动脉介入术（PCI）后炎症因子及主要不良心脏事件（MACE,包括复发心绞痛、急性心肌梗死、严重心律失常、心力衰竭、冠心病死亡）影响.方法纳入60例行PCI的ACS患者,随机分为常规治疗组（n=30）和芪参益气滴丸联合常规治疗组（芪参组,n=30）,采用酶联反应吸附法（ELISA法）比较两组术后24h和术后6个月血清高敏C反应蛋白（hs-CRP）、可溶性CD40配体（sCD40L）及基质金属蛋白酶-9（MMP-9）水平变化,并比较两组6个月MACE事件发生率.结果术后24h两组血清hs-CRP、sCD40L和MMP-9水平均无统计学差异（P＞0.05）;6个月后,两组hs-CRP、sCD40L和MMP-9水平分别是3.18±0.71mg/l、5.86±2.01 ng/dl和240.56±60.6 ng/dl.与对照组相比,芪参组血清hs-CRP、sCD40L及MMP-9均明显降低,差异有统计学意义（P＜0.05）,随访6个月,芪参组MACE发生率较对照组更低（13.33% vs.26.67%,P＜0.05）,且差异有统计学意义.结论 芪参益气滴丸可降低介入术后炎症因子hs-CRP、SCD40L和MMP-9的水平,同时降低MACE近期发生率.     

Clinical implications of elevated serum interleukin-6, soluble CD40 ligand, metalloproteinase-9, and tissue inhibitor of metalloproteinase-1 in patients with acute ST-segment elevation myocardial infarction

BACKGROUND: Atherosclerosis is widely accepted as a chronic inflammatory disease. Research paid much attention to sensitive specific serum biomarkers for vulnerable plaques. The markers not only serve as diagnostic tools for the identification of patients with acute coronary syndrome (ACS), but also help us to identify high-risk patients. However, the existing data are limited and have been conflicting. HYPOTHESIS: Circulating interleukin-6 (IL-6), soluble CD40 ligand (sCD40L), metalloproteinase-9 (MMP-9), and tissue inhibitor of metalloproteinase-1 (TIMP-1) might correlate with the onset and the cardiac mortality of patients with ST-segment elevation myocardial infarction (STEMI). METHODS: Serum levels of IL-6, sCD40L, MMP-9, and TIMP-1 were measured by sandwich enzyme-linked immunosorbent assay (ELISA) in 263 patients with STEMI and 262 age- and gender-matched control subjects without coronary artery disease (CAD). The patients with STEMI were then followed prospectively for 24 mo for the occurrence of cardiac mortality. RESULTS: Compared with the control subjects, patients with STEMI exhibited higher levels of IL-6 (p < 0.001), sCD40L (p < 0.001), MMP-9 (p < 0.001), TIMP-1 (p = 0.045), and MMP-9/TIMP-1 ratio (p = 0.007). Significant and positive correlations between MMP-9 and TIMP-1 (r = 0.610, p相似文献   

Relationship between plasma inflammatory markers and platelet aggregation in patients with clopidogrel resistance after angioplasty

We evaluated the relationship between plasma inflammation markers and clopidogrel resistance in patients after stent implantation. The plasma levels of C-reactive protein (CRP), P-selectin, platelet soluble CD40 ligand (sCD40L), interleukin 6 (IL-6) and platelet aggregation were measured in 352 patients undergoing percutaneous coronary intervention (PCI) at baseline and after 6 months. The plasma levels of CRP, P-selectin, sCD40L, IL-6 was higher in 65 (18.5%) patients with clopidogrel resistance than in those with normal responsiveness at 6 months after PCI. There was a significant positive correlation between soluble CD40L levels and platelet aggregation (r = .28, P < .05). Diabetes (DM) and sCD40L level were independent predictors for unresponsiveness after stent implantation according to stepwise multivariate analyses. The hazard ratio (HR) for sCD40L level was 3.02 (95% CI = 1.28 to 3.25; P = .036) and for DM 2.53 (95% CI = 1.28 to 6.55, P = .03). We conclude that sCD40L and DM may influence clopidogrel resistance.     

主动脉内球囊反搏对急性心肌梗死合并心源性休克老年患者介入术后炎性因子的影响

目的评价主动脉内球囊反搏(IABP)对急性心肌梗死(AMI)合并心源性休克老年患者PCI后炎性因子可溶性CD40配体(sCD40L)的影响。方法选择90例AMI合并心源性休克老年患者分为治疗组42例(IABP行PCI)和对照组48例(直接行PCI);分别测定入院时以及第1、7天的sCD40L水平;比较2组PCI术后1周、3个月的LVEF,随访患者术后6个月的主要不良心脏事件。结果治疗组第1、7天的sCD40L水平明显低于对照组[(3.19±0.39)μg/Lvs(3.51±0.42)μg/L,(2.98±0.34)μg/Lvs(3.12±0.41)μg/L,P<0.05];治疗组患者术后1周、3个月的LVEF较对照组明显改善[(36.11±6.31)%vs(30.26±5.48)%,(44.69±5.02)%vs(41.52±4.17)%,P<0.05)];而2组术后6个月的主要不良心脏事件比较,差异无统计学意义(P>0.05)。结论 AMI合并心源性休克的老年患者,急诊PCI术前采用IABP辅助支持治疗能明显降低术后sCD40L水平,能有效地改善左心室功能,并且安全有效。     

Association between circulating level of CD40 ligand and angiographic morphologic features indicating high-burden thrombus formation in patients with acute myocardial infarction undergoing primary coronary intervention.

BACKGROUND: This study tested the hypothesis that in the acute phase of myocardial infarction (MI), the circulating level of soluble CD40 ligand (sCD40L), an index of platelet activation, is predictive of angiographic morphologic features that indicate high-burden thrombus formation (HBTF) in the infarct-related artery (IRA). METHODS AND RESULTS: This prospective study included 162 consecutive patients: 64 with HBTF and 98 with low-burden thrombus formation (LBTF). All patients had a Killip's classification相似文献   

急性冠脉综合征中CD40L 和基质金属蛋白酶致病作用的研究

目的 探讨CD40L和基质金属蛋白酶（MMP）在冠脉斑块形成中的作用机制。方法 对59例冠状动脉造影证实,有冠状动脉狭窄的急性冠脉综合症患者（男31例,女28例,平均年龄60.3岁）,分为不稳定型心绞痛组（n=32）、急性心肌梗死组（n=27）,同时设正常对照组（体检健康者,n=30）。采用ELISA法检测血清CD40L、C反应性蛋白（CRP）、MMP-2和MMP-9的水平。结果 与正常对照组比较,血清CD40L、CRP、MMP-2和MMP-9的水平,随病情的加重而升高且差异显著（P<0.01）,多支病变者的水平高于单支病变者。血清MMP-2与MMP-9的水平、CD40L与MMP-9的水平均呈正相关（r值分别为0.71和0.78）。结论 血清MMP-2和MMP-9水平的增高与冠脉斑块的形成有一定的联系。CD40L可能是通过MMP-s引起冠脉损伤,从而导致斑块形成和冠心病的发生发展。     

Inverse correlation between soluble CD40 ligand and soluble CD40 is absent in patients with unstable angina

The CD40/CD40 ligand (CD40L) system mediates inflammatory processes important in atherogenesis and plaque instability. The expression of CD40L on activated T cells was suppressed by soluble CD40 (sCD40) in vitro. However, the relationship between soluble CD40L (sCD40L) and sCD40 in unstable angina (UA) is still unknown. Thirty-seven consecutive patients with recent chest pain or discomfort were recruited. Patients with both Braunwald's class IB–IIIB and with coronary stenosis (or stenoses) of >75% were assigned to the UA group (n = 19, aged 67.2 ± 8.2 years), and the rest to the control group (n = 18, aged 63.4 ± 8.7 years). The serum levels of sCD40L and sCD40, and the plasma levels of matrix metalloproteinase (MMP)-9, were measured by enzyme-linked immunosorbent assays. A significantly inverse correlation between sCD40L and sCD40 was shown in the controls (r = −0.72, P = 0.0007), but was absent in the UA group (r = −0.16, P not significant), although there was no statistical significance between these groups in terms of serum levels of sCD40L or sCD40. The difference of the regression slopes of these regression lines was statistically significant (P < 0.01). Additionally, there was a significant correlation between sCD40 and plasma levels of MMP-9 in the patients with and without UA (r = 0.58, P = 0.0096), but no significant correlation between sCD40L and MMP-9 levels (r = 0.00, P not significant). The balance between CD40 and CD40L may be lost in patients with UA. Soluble CD40 expression may also be related to MMP-9 expression in atherosclerotic tissues.     

Plasma matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-2, and CD40 ligand levels in patients with stable coronary artery disease

Endogenous matrix metalloproteinases (MMPs) and their inhibitors, tissue inhibitor of metalloproteinases (TIMPs), are important mediators of extracellular matrix remodeling, which is integral to plaque progression in coronary artery disease. In addition, high levels of the soluble fragment of CD40 ligand (sCD40L) have previously been associated with adverse cardiovascular outcomes. We hypothesized that circulating levels of MMP-9, TIMP-1, TIMP-2, and sCD40L were abnormal in patients who had stable coronary artery disease, and these levels were compared with those in matched controls. We also hypothesized correlations of MMPs, TIMPs, and sCD40L to each other and to high-sensitivity C-reactive protein (a proinflammatory marker), white blood cell count, severity of coronary artery disease (based on angiographic measurements of atherosclerotic burden), and coronary collateralization. We studied 204 adult patients who attended our unit for outpatient diagnostic cardiac catheterization for the investigation of suspected coronary artery disease. Coronary angiograms were scored for atheroma burden and stenosis by 2 independent observers. Circulating levels of MMP-9, TIMP-1, TIMP-2, and sCD40L were measured by enzyme-linked immunosorbent assay. Plasma levels of MMP-9 (p = 0.0099), TIMP-2 (p = 0.0019), and sCD40L (p <0.001), but not TIMP-1 (p = 0.463) were high in patients compared with healthy controls. In patients who had coronary artery disease, MMP-9 and high-sensitivity C-reactive protein levels were significantly higher in women than in men. Only MMP-9 correlated modestly with total white blood cell count (Spearman's correlation, r = 0.274, p = 0.002). Logistic regression of cardiovascular risk factors showed that only white blood cell count was independently associated with MMP-9 (p = 0.02). After standardizing for atheroma and stenosis scores, there were no statistically significant differences in our research indexes in patients who had angiographic collaterals compared with those who did not. In conclusion, stable coronary artery disease is associated with abnormal circulating levels of MMP-9, TIMP-2, and sCD40L, which do not appear to related to each other or to severity of coronary artery disease or collateralization. The gender difference in high-sensitivity C-reactive protein and MMP-9 levels may provide insight into the pathophysiology of coronary artery disease in men and women, and further studies are warranted to explore this potential link.     

急性冠脉综合征患者血浆sCD40L与血清基质金属蛋白酶水平的变化及其意义

目的：观察急性冠脉综合征（ACS）患者可溶性CD40配体（sCD40L）及血清基质金属蛋白酶-9（MMP-9）、血清组织金属蛋白酶抑制物-1（TIMP-1）水平变化及其相关性。方法：采用酶联免疫吸附法测定70例冠心病患者[ACS患者35例、稳定型心绞痛（SAP）患者35例]、35例非冠心病患者（正常对照组）sCD40L、MMP-9、TIMP-1的水平。结果：与正常对照组及SAP组比较,ACS组sCD40L[（2.73±0.92）μg/ml比（3.05±0.98）μg/ml比（4.72±1.15）μg/ml]、MMP-9[（152.38±54.22）ng/ml比（341.12±69.96）ng/ml比（574.2±139.20）ng/ml]水平明显升高（P均〈0.01）,而TIMP-1[（415.92±13.96）ng/ml比（249.32±36.80）ng/ml比（172.20±40.10）ng/ml]水平明显降低（P〈0.01）;且MMP-9与sCD40L呈正相关（r=0.42,P〈0.05）。结论：急性冠脉综合征患者可溶性CD40配体、血清基质金属蛋白酶-9水平升高,血清组织金属蛋白酶抑制物-1水平下降提示这两指标与粥样斑块不稳定相关,可作为判断粥样斑块不稳定的血清学指标。     

Inflammatory-destructive biomarkers of atherosclerotic plaques instability. Study of arterial wall and blood

Concentrations of tumor necrosis factor, interleukin 1- and its receptor antagonist, IL-6, IL-8, IL-18, IL-2, ligand of CD40 receptor (CD40L), high sensitive C-reactive protein (hsCRP), monocyte chemotactic protein -1, endothelial monocyte activating protein II, adhesive molecules (sICAM-1 and sVCAM-1), matrix metalloproteinase (MMP-3, MMP-7, MMP-9), tissue inhibitor of metalloproteinase (TIMP-1) and endothelin-1 were studied in blood and in coronary artery intima/media of men with coronary atherosclerosis without acute coronary syndrome. Blood levels of hsCRP, IL-8, IL-6 and CD40L were higher, while blood levels of sVCAM and TIMP-1 were lower in men with prevalence of unstable atherosclerotic plaques compared to men with prevalence of stable atherosclerotic plaques in coronary arteries. Blood levels of hsCRP, IL-6 and IL-8 correlated with characteristics of coronary artery atherosclerotic plaques instability. Correlation between hsCRP blood level and hsCRP concentration in coronary artery intima/media material was also revealed.     

Elevation of plasma matrix metalloproteinase-9 in the culprit coronary artery in patients with acute myocardial infarction: clinical evidence from distal protection.

BACKGROUND: Although the elevation of circulating plasma matrix metalloproteinase (MMP)-9 levels in patients with acute myocardial infarction (AMI) has been documented, the origin of MMP-9 remains unclear. METHODS AND RESULTS: Plasma MMP-9 levels in both the peripheral circulation and coronary arteries were measured in patients with AMI (n=23) and with stable angina pectoris (SAP, n=10) during percutaneous coronary intervention (PCI) with a distal protection device. Blood samples were collected from the femoral artery (FA) and the coronary artery before (Initial) and after (Second) dilation of the culprit lesion. Coronary sinus blood samples were obtained immediately after PCI (n=7). Coronary artery plaque fragments were aspirated in patients with AMI (n=20) and compared with those from patients with SAP who underwent directional atherectomy (n=10). MMP-9 levels in Initial and Second were significantly higher in patients with AMI than in patients with SAP (p<0.01). In AMI patients MMP-9 levels were significantly higher in Initial than in the FA (p<0.05), and were further increased in Second (p<0.0001), whereas those in the coronary sinus were similar to the FA. Immunohistochemistry revealed augmented MMP-9 expression in the coronary artery plaque fragments from AMI patients. CONCLUSIONS: MMP-9 is mainly released into the coronary circulation from the coronary artery plaque in patients with AMI.     

Increase in Interleukin-6 in the First Hour after Coronary Stenting: An Early Marker of the Inflammatory Response

Background: Inflammation after coronary stenting presages adverse outcomes after percutaneous coronary intervention (PCI). While changes in inflammatory markers have been defined 24–72 hours after PCI, potential changes during the first few hours have not. This study was designed to determine if a systemic inflammatory response could be measured within the first hour after stenting. Methods: Patients (n = 25) undergoing coronary stenting, with predominantly (n = 23) acute coronary syndromes were enrolled prospectively in this registry. Blood samples were collected before PCI, and 10 minutes, 1 hour and 18–24 hours later. No patient received a glycoprotein IIb-IIIa inhibitor. Concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), and interleukin-1 receptor antagonist (IL-1Ra) and soluble CD40 ligand (sCD40L) were measured using ELISA. Results: CRP and sCD40L did not change in the first hour after stenting. By contrast, IL-6 increased in the first hour (before = 7.6 ± 7.7 pg/ml, 1 hour = 12 ± 12 pg/ml; p < 0.001). The concentration of IL-1Ra tended to be greater after 1 hour (before = 426 ± 261 pg/ml, 1 hour = 511 ± 406 pg/ml; p = 0.11). Increase in IL-1Ra was apparent only in female subjects (p = 0.004 for the difference in trend between the two genders). A correlation was not observed between the increase in IL-6 at 1 hour and the increase in CRP at 24 hours (r = –0.21). Conclusions: In patients undergoing coronary stenting, increase in IL-6 can be detected 1 hour after PCI, and thus IL-6 may be an early initiator of the systemic inflammatory response to stenting.     

Comparison of platelet function and morphology in patients undergoing percutaneous coronary intervention receiving bivalirudin versus unfractionated heparin versus clopidogrel pretreatment and bivalirudin

We hypothesized that direct thrombin inhibition could attenuate platelet activation and release of soluble CD40 ligand (sCD40L), a marker of inflammation, during percutaneous coronary intervention (PCI). To assess platelet function under flow conditions with bivalirudin versus unfractionated heparin (UFH), we employed the cone and plate(let) analyzer (CPA) assay in drug-spiked blood samples from volunteers (n = 3) in vitro, and then in PCI patients who received bivalirudin alone (n = 20), UFH alone (n = 15), and clopidogrel pretreatment plus bivalirudin (n = 15). Scanning electron microscopy was employed to image bivalirudin or UFH-treated platelets to determine whether platelet function observations had a morphologic explanation. Enzyme immunoassay was used to measure sCD40L levels in PCI patients. In vitro, bivalirudin decreased platelet surface coverage; UFH increased platelet surface coverage. In PCI patients, bivalirudin alone decreased platelet surface coverage, UFH alone increased platelet surface coverage, and clopidogrel pretreatment plus bivalirudin additively reduced platelet surface coverage. Unlike UFH, bivalirudin did not activate platelets in SEM studies. Bivalirudin alone or coupled with clopidogrel significantly reduced plasma sCD40L in PCI patients. In conclusion, our findings suggest that under flow conditions, bivalirudin alone or coupled with clopidogrel may have an antiplatelet effect versus UFH alone during PCI. These data suggest that bivalirudin and UFH may confer an anti-inflammatory effect by reducing sCD40L during PCI.     

Prognostic value of interleukin-6 during a 3-year follow-up in patients with acute ST-segment elevation myocardial infarction

Accumulating evidence suggests that inflammation plays an essential role in the pathogenesis of atherosclerosis. This recognition has stimulated the evaluation of different inflammatory markers as potential predictors of cardiovascular risk. However, the existing data are limited and controversial. This study was designed to simultaneously measure serum levels of interleukin-6 (IL-6), soluble CD40 ligand (sCD40L), metalloproteinase-9 (MMP-9), and tissue inhibitor of metalloproteinase-1 (TIMP-1) in patients with acute ST segment elevation myocardial infarction (STEMI) and to evaluate their ability to predict prognosis. A prospective cohort study was conducted with 263 patients with first STEMI who were admitted to our institute within 6 h of symptoms onset. Clinical data were recorded and serum admission levels of IL-6, sCD40L, MMP-9, and TIMP-1 were measured by sandwich enzyme-linked immunosorbent assay. The patients were then followed prospectively for the occurrence of cardiovascular mortality for 3 years. Follow-up information was available for 228 patients (86.7%) from the 263 STEMI patients; 34 patients died from cardiovascular causes during the 3-year follow-up period. Kaplan-Meier plots demonstrated a significant increase in cardiovascular mortality with increasing IL-6 levels (χ² = 14.13, P = 0.0002, by log-rank test). Logistic regression analysis revealed that IL-6 was an independent predictor for cardiovascular mortality. The present study indicates that elevated admission level of IL-6 could provide valuable information for long-term risk stratification in patients with STEMI.     

Systemic versus coronary levels of inflammation in acute coronary syndromes

To address a possible link between systemic and coronary inflammation in the setting of acute coronary syndromes, the authors examined both levels of 3 inflammatory mediators such as high sensitive C-reactive protein (hs-CRP), interleukin (IL)-6, and matrix metalloproteinase (MMP)-9 in patients with the early phase of acute myocardial infarction (AMI). In total, 20 patients with AMI showing minimal elevation of cardiac enzymes were studied. Before angioplasty, peripheral blood and culprit coronary thrombus were sampled to compare systemic and coronary levels of hs-CRP, IL-6, and MMP-9. Relation of systemic levels of hs-CRP and IL-6 to culprit coronary morphology was also evaluated by the use of intravascular ultrasound. Systemic and coronary levels of hs-CRP were nearly equivalent (4.3 +/- 5.0 vs 4.7 +/- 5.4 mg/L, p = 0.279), whereas IL-6 and MMP-9 showed higher in coronary levels than in systemic levels (169 +/- 154 vs 93 +/- 107 microg/mL, p = 0.002 and 164 +/- 116 vs 103 +/- 94 ng/mL, p = 0.018, respectively). Systemic levels of hs-CRP were correlated with coronary levels of IL-6 (r = 0.566, p = 0.009). Culprit coronary plaque area demonstrated a positive relation with systemic levels of hs-CRP (r = 0.466, p = 0.038) and also IL-6 (r = 0.707, p <0.001). The present study may provide an important insight into the link between systemic and coronary levels of inflammation, which is also associated with vulnerable coronary morphology in the setting of acute coronary syndromes.     

Phase I study of eptifibatide in patients with sickle cell anaemia

The α IIb β 3 antagonist eptifibatide is an effective treatment for patients with acute coronary syndromes (ACS). Platelet reactivity and CD40 ligand (CD40L) may play a role in the pathophysiology of sickle cell anaemia (SCA) similar to that in ACS, suggesting that inhibition of platelet aggregation and CD40L release by eptifibatide may benefit patients with SCA. Following eptifibatide infusion, safety and pharmacodynamic data were obtained from four SCA patients in their non-crisis, steady states. Eptifibatide was well tolerated, with no adverse changes in the haematological, biochemical or coagulation parameters studied. Eptifibatide did not increase plasma levels of platelet factor 4 or beta-thromboglobulin, P-selectin exposure or platelet:leucocyte aggregate formation. Moreover, decreases in platelet aggregation and soluble CD40L (sCD40L) levels achieved in SCA patients were comparable to those observed in the treatment of ACS. Finally, indicators of inflammation, macrophage inflammatory protein-1 α , tumour necrosis factor- α and myoglobin were reduced following eptifibatide infusion, while vasodilation correlatives, matrix metalloproteinases (MMP-2 and MMP-9) and leptin were increased. Based on these phase I results, eptifibatide may benefit SCA patients by inhibiting platelet aggregation, decreasing sCD40L levels and favourably altering plasma levels of inflammatory mediators.     

替罗非班对老年急性冠状动脉综合征介入治疗后血清可溶性CD40配体的影响

目的观察替罗非班在老年非ST段抬高急性冠状动脉综合征（NSTEACS）介入治疗（PCI）的疗效及对血清可溶性CD40配体（sCD40L）水平的影响。方法将80例经危险度分层为高危的老年NSTEACS患者行介入治疗,随机分为替罗非班组43例,对照组37例,观察住院期间及术后30d内的主要心血管事件（MACE）,用酶联免疫吸附法（ELISA）法测定所有入选患者PCI前后血清sCD40L水平。结果与对照组相比,替罗非班组住院期间及术后30d内MACE发生率有所降低（9.5%比18.9%,P〉0.05） 两组大出血发生率均为0,差异无统计学意义 替罗非班组轻度出血（10/43）较对照组（7/37）有所增加,但差异无统计学意义（P〉0.05） 替罗非班组治疗后血清sCD40L水平较对照组显著降低（3.17±1.01μg/L比4.05±0.96μg/L,P〈0.01）。结论替罗非班可降低MACE发生率,在老年NSTEACS患者PCI中疗效确切,能显著降低sCD40L的水平。     

不同炎性标志物对冠状动脉病变的预测价值

目的 探讨可溶性CD40L、单核细胞趋化蛋白1、白细胞介素8和白细胞介素6等炎性标志物对冠状动脉病变严重程度和稳定性的预测价值.方法 应用流式细胞术检测129例冠心病患者血浆可溶性CD40L、单核细胞趋化蛋白1、白细胞介素8和白细胞介素6水平,计算各类型冠心病患者冠状动脉病变的Gensini积分,分析上述炎性标志物与Gensini积分的相关关系以及对急性冠状动脉综合征的预测价值.结果 四种炎性标志物血浆浓度在冠心病组均显著高于对照组(P均<0.01),其中可溶性CD40L、单核细胞趋化蛋白1和白细胞介素6的浓度在急性心肌梗死组高于稳定型心绞痛组(P=0.001、P=0.009和P=0.011).血浆单核细胞趋化蛋白1和白细胞介素6水平与冠状动脉Gensini积分呈正相关关系(r=0.322, P<0.00001;r=0.203,P=0.026);多因素Logistic回归分析显示白细胞介素6对急性冠状动脉综合征有预测价值(OR=1.275,P=0.037).结论 血浆可溶性CD40L、单核细胞趋化蛋白1、白细胞介素8和白细胞介素6等炎性标志物与冠状动脉粥样硬化病变有关;血浆单核细胞趋化蛋白1和白细胞介素6能反映冠状动脉病变的严重程度;白细胞介素6对预测冠状动脉病变不稳定的冠心病急性冠状动脉综合征有一定价值.