冠状动脉斑块形态学与血浆炎症介质的关系

目的从冠状动脉（冠脉）斑块的影像学、血浆炎症介质水平等方面综合评价冠脉斑块易损性。方法将冠脉造影显示为单支病变的58例患者,按造影结果分为Ⅰ型病变组（16例）、Ⅱ型病变组（25例）、Ⅲ型病变组（17例）及对照组（17例）。其中行血管内超声（IVUS）检查的28例患者分为急性冠脉综合征（ACS）组和稳定性心绞痛组2个亚组。采用酶联免疫吸附法测定血浆高敏C反应蛋白（hs-CRP）、金属基质蛋白酶（MMP,包括MMP-2、MMP-9）、CD40配体（CD40L）和妊娠相关蛋白-A（PAPP—A）水平。结果Ⅱ型病变组血浆MMP-2、MMP-9和PAPP—A水平显著高于Ⅰ型病变组（P〈0．05）、Ⅲ型病变组（P〈0．05）和对照组（P〈0．001）;线性相关分析显示,Ⅱ型病变组hs—CRP与MMP-2显著正相关（r=0．508）;MMP-2与MMP-9、CD40L、PAPP—A显著正相关（r=0．647、0．704、0．751）;MMP-9与CD40L、PAPP—A显著正相关（r=0．491、0．639）;CD40L与PAPP—A（r=0．896）显著正相关。IVUS亚组分析表明,ACS组的“罪犯”病变斑块面积、斑块负荷、高危斑块发生率、重构指数和正重构均显著大于对照组（P=0．000、0．037、0．028、0．015和0．040）;ACS组血浆hs—CRP、MMP-2、MMP-9和PAPP-A水平也显著升高（P：0．033、0．000、0．000和0．027）。结论冠脉造影、IVUS检查结合检测血浆炎症介质水平更有助于判断冠脉斑块的易损性。     

炎性因子在急性心肌梗死发病中的作用及不同剂量他汀类药物对其影响

目的研究炎性因子在急性心肌梗死发病中的作用及早期应用不同剂量辛伐他汀对急性心肌梗死患者稳定斑块、减少炎症反应的作用。方法将61例急性心肌梗死患者随机分为他汀治疗1组(辛伐他汀20mg/d,n=21)、他汀治疗2组(辛伐他汀80mg/d,n=23)和常规治疗组(不服用任何调脂药物,n=17);于发病48h内和治疗1周后分别测定血清CD40L、基质金属蛋白酶-9(MMP-9)、C-反应蛋白(CRP)水平。另设健康对照组(n=35)与之对照。结果①治疗前急性心肌梗死组的血清CD40L、MMP-9、CRP水平均较健康对照组明显增高(P<0.01)。②急性心肌梗死三组治疗前血浆CD40L、MMP-9和CRP水平差异无统计学意义,常规治疗组治疗后CD40L、MMP-9和CRP水平较治疗前分别降低12%、13%、6%,治疗前后比较差异无统计学意义。他汀治疗1组治疗后CD40L、MMP-9和CRP水平分别降低31%、42%、29%,治疗前、后比较差异有统计学意义(P<0.05)。他汀治疗2组治疗后CD40L、MMP-9和CRP水平分别降低52%、68%、67%,治疗前、后比较差异有统计学意义(P<0.001)。③急性心肌梗死各组在治疗前、后血脂各组分大致相近,差异无统计学意义。结论急性心肌梗死患者存在着动脉粥样硬化斑块不稳定及炎症加速的过程。早期应用大剂量他汀药物,可明显降低血清炎症因子水平,减少患者冠状动脉粥样斑块基质成分的降解和炎症反应,具有稳定斑块作用。     

64层CTA结合血清MMP-9、sCD40L评价冠脉临界病变斑块成分及稳定性

目的:通过64层计算机体层摄影冠状动脉血管造影识别冠状动脉临界病变患者的冠脉斑块成分,并检测血清基质金属蛋白酶-9（MMP-9）、可溶性CD40配体（sCD40L）水平,探讨其斑块稳定性及临床意义。方法: 选择经64层计算机体层摄影冠状动脉血管造影证实至少有1支冠脉某一阶段狭窄30%～70%的患者65例,其中稳定型心绞痛36例,不稳定型心绞痛29例,通过斑块CT值及冠脉管腔碘造影剂CT值确定其斑块类型:非钙化斑块,钙化斑块和混合斑块;并用ELISA方法测定患者及37例无心血管疾病对照组血清MMP-9、sCD40L水平,比较其差异性并探讨其相互关系。结果: 冠脉临界病变患者混合斑块最多,其次为非钙化斑块,钙化斑块最少,“混合斑块+非钙化斑块”显著多于钙化斑块数目;患者血清MMP-9、sCD40L水平显著高于无心血管疾病对照组。结论: 冠心病冠脉临界病变斑块多为易损斑块。     

斑块稳定性与炎症反应在急性冠状动脉综合征中作用的研究

目的 探讨冠状动脉（冠脉）粥样斑块稳定性和炎症反应在急性冠状动脉综合征（ACS）中的作用。方法 对28例ACS和13例稳定性心绞痛（SA）患者“罪犯”冠脉进行血管内超声（IVUS）检查,同时测定外周血清高敏C反应蛋白（hs-CRP）、基质金属蛋白酶-9（MMP-9）、组织型基质金属蛋白酶抑制剂-1（TIMP-1）、可溶性CD40L（sCD40L）含量。结果 ACS患者冠脉病变处以软斑块为主71．4％（20／28）,SA患者冠脉病变处以硬斑块为主76．9％（10／13）,差异有统计学意义（P=0．004）。与sA组比较,ACS组病变处斑块面积大（P=0．004）、斑块负荷重（P=0．048）、以正性重构为主（P=0．013）。ACS组血清hs—CRP、MMP-9、sCIMOL含量均高于SA组,TIMP-1含量在ACS组和SA组之间差异无统计学意义（P=0．234）,ACS组hs-CRP与MMP-9（r=0．671,P=0．000）、sCIMOL（r=0．494,P=0．008）呈正相关。结论 冠脉“罪犯”病变处结构性易损斑块是ACS发作基础,CIMOL和MMP-9参与的炎症反应导致斑块功能性不稳定和不同临床表现。     

CD40L和MMPs与冠脉支架介入治疗术后冠脉再狭窄的相关性及其临床意义

目的: 观察CD40L和基质金属蛋白酶（MMPs）与冠脉支架介入治疗术后冠状动脉再狭窄的关系，并分析CD40L和MMPs检测的临床意义。方法: 选择330例行冠脉支架置入术冠心病患者。对所有患者分别于术前，术后1个月，6个月，1年，采用ELISA法测定CD40L、C反应蛋白（CRP）、MMP-2、MMP-9。按照冠状动脉狭窄评分（CSA），再将32例支架术后再狭窄患者分为Ⅰ、Ⅱ、Ⅲ 3组。结果: 冠状动脉狭窄患者术后1个月，6个月，1年CD40L、CRP， MMP-2、MMP-9等较术前均有显著降低，术后再狭窄患者上述指标增高明显，随病情加重而升高，CSA积分越高上述指标增高越明显。MMP-2、MMP-9与CD40L呈正相关性（分别为r=0.51，r=0.64）。结论: CD40L和MMPs与支架术后冠状动脉再狭窄形成有一定的相关性，CD40L和MMPs的检测，有助于冠脉支架术后临床疗效的评价。     

急性冠脉综合征患者血清高敏C反应蛋白、基质金属蛋白酶-9与冠状动脉病变程度的相关性研究

目的 探讨急性冠脉综合征患者血清高敏C反应蛋白（hs-CRP）、基质金属蛋白酶-9（MMP-9）与冠状动脉病变程度的关系.方法 将88例急性冠脉综合征患者依据冠状动脉造影结果分为单支病变组（30例）、双支病变组（28例）和多支病变组（30例）,并选择同期冠状动脉造影检查正常者32例为对照组,比较各组hs-CRP、MMP-9的差异,运用Syntax评分评价急性冠脉综合征患者冠状动脉病变程度,通过多元逐步回归分析Syntax评分与各临床资料的相关性.结果 急性冠脉综合征患者血清hs-CRP、MMP-9水平明显高于对照组,并且随着冠状动脉病变严重程度的增加,hs-CRP、MMP-9水平逐渐升高（P＜0.05）.Pearson相关分析显示,hs-CRP与MMP-9呈正相关（r =0.438,P＜0.05）.多元逐步回归分析提示,Syntax评分与hs-CRP、MMP-9水平呈正相关（r分别为0.41和0.57,P＜0.05）.结论 急性冠脉综合征患者血清hs-CRP、MMP-9水平与冠状动脉病变程度相关,冠状动脉病变程度越重血清中hs-CRP、MMP-9的水平越高.     

不稳定型心绞痛患者血清MMP-9与sCD40L水平变化及意义

本文36例不稳定型心绞痛（UA）患者（UA组）,35例稳定型心绞痛（SA）患者（SA组）,32例健康人（对照组）.采用酶联免疫吸附法测定三组血清基质金属蛋白酶-9（MMP-9）及可溶性细胞表面分化抗原40配体（sCD40L）水平.发现UA组入院时sCD40L及MMP-9水平均明显高于SA组及对照组（P＜0.01）.MMP-9和C反应蛋白（CRP）呈正相关关系（r=0.643,P＜0.01）.UA组病情稳定后,血清sCD40L、MMP-9水平较入院时明显降低（P＜0.01）.UA组有7例发生急性冠状动脉事件,SA组未发现.提示在UA发生、发展和病情恶化中,MMP-9和sCD40L起重要作用,sCD40L可能通过促使MMP-9的表达而促发急性冠脉综合征.     

MMP-2、MMP-9和hs-CPR与急性冠脉综合征关系的研究

目的探讨基质金属蛋白酶2（MMP-2）、基质金属蛋白酶9（MMP-9）和超敏C-反应蛋白（hs-CPR）在急性冠脉综合征（ACS）中的变化及对预后的影响。方法选择2006年3月～2010年5月住院的ACS患者120例为观察组;其中不稳定型心绞痛（UA）40例、无ST段抬高心肌梗死（NSTEMI）40例、急性ST段抬高心肌梗死（STE-MI）40例。另选择同期稳定心绞痛患者40例为对照组,采用酶联免疫吸附法测定MMP-2、MMP-9水平,用免疫散射比浊法测定hs-CRP水平,并分析MMP-2、MMP-9及hs-CRP的变化和冠脉病变之间的关系。结果观察组血清MMP-2、MMP-9及hs-CRPR水平高于对照组（P〈0.05）,NSTEMI组和STEMI组血清MMP-2、MMP-9及hs-CRP的水平高于UA组（P〈0.05）;观察组患者血清MMP-2与hs-CRP无明显相关性（r=0.25,P〉0.05）,而血清MMP-9与hs-CRP水平呈正相关（r=0.599,P〈0.05）。结论联合检测ACS患者血清MMP-2、MMP-9和hs-CRP对判断斑块稳定性、预测ACS的危险分层及预后有重要的指导意义。     

血清CD40、CD40L和基质金属蛋白酶-9水平与颈动脉内膜中层厚度的相关性

目的观察颈动脉粥样硬化(CAS)患者颈动脉内膜中层厚度(IMT)、白细胞分化抗原40及其配体(CD40/CD40L)和基质金属蛋白酶9(MMP-9)变化,探讨上述指标之间的关系。方法选择CAS患者94例,其中IMT增厚的有34例,颈动脉斑块形成的有60例;健康体检者20例(IMT正常组)。采用颈动脉超声检测实验组和对照组IMT,采用酶联免疫吸附试验(ELISA)法检测两组血清CD40、CD40L和MMP-9水平。结果随着IMT的增厚,血清CD40、CD40L、MMP-9水平明显升高(P0.05);有不稳定斑块的CAS患者IMT及血清CD40、CD40L、MMP-9水平较稳定斑块患者明显升高,不稳定斑块CAS患者脑梗死(CI)发病率高于斑块稳定组(P均0.05)。结论血清CD40、CD40L、MMP-9能促进CAS的形成和增厚,MMP-9能增加斑块的不稳定性,导致CI的发生,监测血清CD40、CD40L、MMP-9水平,能用来预测CAS患者的IMT、斑块的稳定性和疾病的预后。     

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。     

Association between plasma inflammatory markers and morphology of coronary artery lesion in patients with coronary artery disease

The atherosclerotic plaque vulnerability may be related to inflammation,immunity,metabolism and blood clotting.One of the key factors affecting plaque stability is inflammatory reaction.This study was to investigate the relationship between vulnerability of coronary artery plaque evaluated with coronary angiography (CAG),intravascular ultrasound (IVUS) and the levels of plasma inflammatory markers.Methods Fifty-eight consecutive patients with acute coronary syndrome who had coronary lesion of a single vessel were divided into 3 groups based on angiographic morphology of the lesions:type Ⅰ lesion group (n =16),type Ⅱ lesion group (n =25) and type Ⅲ lesion group (n =17).The control group consisted of 17 patients with stable angina.Plasma levels of high sensitivity C reaction protein (hs-CRP),matrix metalloproteinase (MMP,including MMP-2 and MMP-9),CD40 ligand (CD40L) and pregnancy associated plasma protein-A (PAPP-A) were measured by ELISA.A subgroup of 28 patients (including 18 ACS patients and 10 stable angina control patients) who underwent IVUS study,were analyzed.Results The plasma levels of MMP-2,MMP-9 and PAPP-A in type Ⅱ lesion group were significantly higher than those in other groups (all P＜0.05).In type Ⅱ lesion group,linear correlation analyses showed significant positive correlation between levels of hs-CRP and MMP-2 (r=0.508);MMP-2 and MMP-9,CD40L,PAPP-A (r=0.647,0.704 and 0.751,respectively);MMP-9 and CD40L,PAPP-A (r=0.491 and 0.639,respectively);CD40L and PAPP-A (r=0.896).IVUS subgroup analysis showed that the area of plaques and plaque burden in culprit lesion,the incidence of high-risk plaques,remodeling index (RI) and positive remodeling percentage in ACS patients were significantly greater than those in control subgroup (P=0.000,0.037,0.028,0.015 and 0.040,respectively).Compared with control subgroup,the plasma levels of hs-CRP,MMP-2,MMP-9 and PAPP-A were markedly elevated (P=0.033,0.000,0.000 and 0.027,respectively).Conclusions CAG and IVUS combined with study on plasma levels of inflammation mediators are helpful in judging the vulnerability of coronary artery plaques.(J Geriatr Cardiol 2008;5:207-211)     

人冠状动脉粥样硬化病灶内CD40L水平与病灶结构变化的关系

目的观察人冠状动脉粥样硬化病灶结构变化、CD40L、基质金属蛋白酶9(MMP-9)蛋白表达水平,探讨CD40/CD40L信号在人冠状动脉粥样硬化发生发展中的作用。方法收集不同程度粥样硬化的人冠状动脉血管60例作为实验组,以12例无病变的人冠状动脉为对照组,常规HE染色观察两组人群冠状动脉的组织结构并用图像分析软件检测病灶结构的相关指标,免疫组织化学染色检测CD40L、MMP-9蛋白表达水平,分析CD40L、MMP-9表达水平与动脉硬化病灶结构变化之间的关系。结果发生粥样硬化的冠状动脉CD40L表达均增强,其表达主要分布于斑块肩部和底部的泡沫细胞。同时病灶内MMP-9表达水平增高并与CD40L水平、病灶大小尤其是坏死灶的大小呈正相关,MMP-9表达水平与纤维帽厚度无明显相关性。随着MMP-9水平增高,纤维帽厚度/内膜最大厚度比值降低。结论人冠状动脉粥样硬化病灶内CD40L、MMP-9表达水平明显增强,CD40L可能通过促进MMP-9表达,使血管病灶内细胞外基质分解加强,从而促进病变的进展及坏死灶的扩大,使粥样病灶稳定性下降。     

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.     

Soluble CD40 ligand and interleukin-6 in the coronary circulation after acute myocardial infarction

BACKGROUND: Inflammation, operated by blood, vascular and immune cells interaction, is implicated in plaque disruption and CD40 ligand (CD40L) was identified on activated T cells and platelets. We sought to investigate the roles of local inflammation in acute myocardial infarction (AMI). METHODS: Coronary sinus (CS) and arterial (A) levels of interleukin (IL)-6 and soluble CD40L (sCD40L) and matrix metalloproteinase (MMP)-9 activity in serial blood samples obtained until 48 h after percutaneous coronary intervention (PCI) were determined. In tissue specimens obtained by aspirating thrombectomy and directional coronary atherectomy, CD40L was immunohistochemically stained. RESULTS: Trans-cardiac gradient (CS-A) of IL-6, indicating cardiac release into the coronary circulation, significantly increased at 24 h after PCI in patients with AMI (group MI, n=17) in contrast with angina pectoris (n=10). Soluble CD40L levels in CS showed earlier peak, yielding trans-cardiac gradient, at 9 h in both groups. The maximum (max) release of IL-6 in MI, but not sCD40L, positively correlated with end-diastolic volume index (R=0.84) and negatively with ejection fraction (R=-0.66) by contrast ventriculography at 6-month follow up. Immunohistological study revealed the expression of CD40L in intra-coronary occlusive and mural thrombi. Aspirating thrombectomy significantly reduced the increase in both sCD40L levels and MMP-9 activity, but not max IL-6 release in MI. CONCLUSIONS: In contrast with myocardial injury represented by IL-6 release, acute rise in sCD40L levels with the MMP-9 activation in the coronary circulation may possibly reflect local inflammation with platelet activation and be a novel marker of plaque damage by PCI.     

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.     

辛伐他汀对不同血脂水平急性冠状动脉综合征患者血清基质金属蛋白酶水平的影响

目的　研究正常血脂和高血脂急性冠状动脉综合征 (ACS)患者应用辛伐他汀对抑制动脉粥样硬化斑块细胞外基质降解 ,减少炎症反应 ,稳定斑块的作用。方法　采用双盲、随机、对照方法 ,将正常血脂 (NC组 )和高血脂 (HC组 )ACS患者分为他汀治疗组 (辛伐他汀 2 0mg d ,共 8周。NC组 ,n =33;HC组 ,n =36 )和他汀对照组 (NC组 ,n =32 ,HC组 ,n =36 ) ;于治疗前后分别测定血清基质金属蛋白酶 (MMP) 1、MMP 9、基质金属蛋白酶抑制因子 (TIMP) 1、MMP 9 TIMP 1、高敏C 反应蛋白(hs CRP)水平。结果　 (1)治疗前NC、HC各组的血清MMP 1、MMP 9、MMP 9 TIMP 1、TIMP 1、hs CRP水平均较健康对照组 (n =6 0 )明显增高 ,与血脂水平不相关。 (2 )经辛伐他汀治疗 8周后 ,两治疗组血清MMP 1、MMP 9、MMP 9 TIMP 1、hs CRP水平均明显降低 ,血清TIMP 1水平无显著性差异。HC他汀治疗组血清总胆固醇 (TC)、甘油三酯 (TG)、低密度脂蛋白胆固醇 (LDL C)水平明显降低 ,高密度脂蛋白质胆固醇 (HDL C)水平略有上升 ;NC他汀治疗组血清TC、LDL C水平明显下降 ,TG、HDL C水平略有上升和下降 ,但无显著差异。结论　在正常血脂和高血脂ACS患者中 ,早期应用他汀治疗 ,可减少斑块基质成分的降解和炎症反应 ,具有稳定斑块作用。