Relationships of adiponectin and matrix metalloproteinase-9 to tissue inhibitor of metalloproteinase-1 ratio with coronary plaque morphology in patients with acute coronary syndrome

OBJECTIVES:

Adiponectin, an adipocyte-specific protein, matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) play a crucial role in arteriosclerosis and plaque disruption. The present study was designed to elucidate the relationship of adiponectin and the ratio of MMP-9/TIMP-1 and their effects on the stability of plaque in acute coronary syndrome (ACS).

METHODS:

The concentrations of adiponectin, MMP-9, TIMP-1 and interleukin-10 were analyzed using ELISA in 56 consecutive unselected patients divided into two groups, stable angina (n=13) and ACS (n=43), and were compared with 19 healthy control subjects. The 56 patients were also angiographically studied and divided into two groups, simple lesion (n=22) and complex lesion (n=34), based on coronary plaque morphology.

RESULTS:

The ratio of MMP-9/TIMP-1 showed significantly higher values in the ACS group compared with the control group (0.22±0.10 versus 0.11±0.03; P<0.001). Adiponectin was negatively correlated with the ratio of MMP-9/TIMP-1 (r=–0.332; P=0.008) and positively correlated with interleukin-10 (r=0.651; P=0.001). Multivariate logistic regression analysis showed that adiponectin (P=0.046) and MMP-9/TIMP-1 (P=0.044) are independent predictors for ACS, and MMP-9/TIMP-1 (P=0.013) is an independent predictor for complex lesion morphology plaques.

CONCLUSION:

In the present study, it was found that adiponectin has a negative relationship with the ratio of MMP-9/TIMP-1 in patients with ACS, and that the ratio of MMP-9/TIMP-1 is an independent predictor of the stability of atherosclerotic plaque and the severity of coronary atherosclerosis.     

急性冠脉综合征患者早期阿托伐他汀治疗对血浆金属蛋白酶-9、C反应蛋白的影响

目的研究急性冠状动脉综合征（ACS）患者早期应用较大剂量阿托伐他汀治疗对抑制动脉粥样硬化斑块细胞外基质降解、减少炎症反应和稳定斑块的作用。方法58例ACS患者随机分为对照组（28例，未服用任何调脂药物）和阿托伐他汀组（30例，20mg／d），测定治疗前后金属蛋白酶-9（MMP-9）、C反应蛋白（CRP）和血脂水平的变化。结果两组治疗前、后血脂各组成分的变化差异均无统计学意义（P〉O．05），而阿托伐他汀治疗组治疗后MMP-9及CRP水平均明显降低，与治疗前比较差异有统计学意义（P〈0．01）。结论ACS患者早期应用大剂量他汀类药物治疗，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。     

基质金属蛋白酶-9与急性冠状动脉综合征的临床相关性研究

目的:探讨血清基质金属蛋白酶 9(MMP 9)与急性冠状动脉综合征(ACS)的关系。方法:经冠状动脉造影(CAG)确诊的冠心病患者85例,其中ACS患者(ACS组)58例,包括急性心肌梗死(AMI)22例,不稳定型心绞痛(UAP)36例;稳定型心绞痛组(SAP组)27 例;另设对照组 24 例。用酶联免疫吸附法(ELISA)测定各病例造影前及行PTCA者术后血清MMP 9浓度。结果:在造影前,ACS组、SAP组及对照组血清 MMP 9 浓度分别为(26.85±6.25)、(17.35±7.12)、(16.83±5.92)μg/L;此外,ACS组内 AMI和 UAP患者血清 MMP 9 浓度分别为(32.56±6.55)、(24.78±5.76)μg/L。AMI及UAP患者与SAP组之间MMP 9浓度差异有统计学意义,SAP组与对照组之间差异无统计学意义;ACS组内,AMI与UAP患者之间差异无统计学意义。血清 MMP 9 水平与C反应蛋白(CRP)、WBC、冠状动脉病变评分、冠状动脉狭窄程度之间呈明显的正相关,与冠状动脉病变支数、肌钙蛋白 I(cTnI)、肌酸激酶同工酶(CK MB)、总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL C)、低密度脂蛋白胆固醇(LDL C)、PLT间无明显相关性。PTCA术后 l d MMP 9 浓度均较术前要明显升高。结论:ACS患者血清MMP 9浓度明显升高,其水平与冠状动脉内粥样硬化斑块的稳定性密切相关,提示其有助于冠心病的危险分层,对评价     

金属蛋白酶9和超敏C反应蛋白与稳定期卒中的相关性

目的 了解缺血性卒中稳定期血基质金属蛋白酶9(MMP-9)和超敏C反应蛋白(hs-CRP)水平及之间的相关性,探讨其可能的临床应用价值.方法 将患者分为卒中复发组(39例)、卒中稳定组(37例)、无症状颅内动脉狭窄组(46例)并设对照组(74例).收集相关临床资料,检测MMP-9和hs-CRP浓度.结果 hs-CRP水平复发组(2.34 mg/L)＞稳定组(1.45 mg/L)＞无症状狭窄组(1.31 mg/L)＞对照组(0.96 mg/L)(P=0.001);MMP-9水平复发组(121.82±72.99)μg/L＞无症状狭窄组(119.18±80.01)μg/L＞稳定组(112.76±59.66)μg/L,三组间差异无统计学意义(P=0.947),比较三组病例组MMP-9平均水平(118.08±71.06)pg/L显著高于对照组[(57.55±10.44)μg/L,P＜0.001];Spearman相关分析显示:MMP-9与hs-CRP之间呈显著正相关(r=0.337,P＜0.001).结论 hs-CRP在卒中稳定期仍维持较高水平,并与卒中复发相关;而MMP-9与动脉粥样硬化相关性强于卒中事件.     

MMP-9、TIMP-1在胰腺癌组织中的表达及临床意义

目的:探讨胰腺癌患者组织中MMP-9、TIMP-1的表达及其相互关系,分析其与临床及转移预后的关系.方法:免疫组织化学SP法检测63例胰腺癌、11例慢性胰腺炎和6例正常胰腺组织中MMP-9、TIMP-1的表达.结果:胰腺癌组织中MMP-9表达明显高于慢性胰腺炎和正常胰腺组织(58.7% vs 18.1%,0.0%;均P<0.05).TIMP-1在胰腺癌的表达低于正常胰腺组织(46.0% vs 100.0%,P<0.05).MMP-9和TIMP-1在胰腺癌组织中的表达与性别、年龄、组织学分级无关,而与患者的淋巴结转移、远处转移情况有关(P<0.05).结论:MMP-9、TIMP-1在胰腺癌组织中的表达变化可能与胰腺癌转移相关.     

辛伐他汀对急性冠状动脉综合征患者早期血浆C-反应蛋白和基质金属蛋白酶-9的影响

目的探讨短期应用辛伐他汀对急性冠状动脉综合征(ACS)患者早期血浆C-反应蛋白(CRP)和基质金属蛋白酶-9(MMP-9)的影响。方法经临床诊断ACS46例,随机分为治疗组和对照组,各23例。对照组给予ACS的一般治疗,不予任何降脂药;治疗组除给予ACS的一般治疗外,加服辛伐他汀40mg/d,共3d。用免疫比浊法和酶联免疫吸附法(ELISA)分别检测2组患者血清CRP和MMP-9。结果2组患者治疗前、后血脂TC、TG、HDL-C、LDL-C的比较差异无统计学意义。2组治疗前和对照组治疗前后的血浆CRP、MMP-9比较差异无统计学意义;治疗组CRP和MMP-9治疗后较治疗前分别下降39.82%和32.39%,均差异有统计学意义(P<0.05)。结论应用辛伐他汀短期治疗ACS患者能够使CRP和MMP-9显著下降,说明他汀类早期应用有抗炎、稳定斑块及防止斑块破裂的作用。     

急性冠状动脉综合征患者血清基质金属蛋白酶-9水平的临床意义

目的　探讨血清基质金属蛋白酶 ( MMP) -9水平与粥样斑块破裂的关系及其作为粥样斑块破裂的血清学指标的意义。方法　急性冠状动脉综合征 ( ACS)组 3 4例 ,其中不稳定型心绞痛 ( UAP) 18例、急性心肌梗死 ( AMI) 16例。稳定型心绞痛 ( SAP)组 3 0例。正常对照组 3 0例。比较 3组之间血清 MMP-9水平的差异。结果　 ACS组血清 MMP-9水平高于 SAP组及正常对照组 ,具有显著性差异。 SAP组血清 MMP-9水平高于正常对照组 ,也具有显著性差异。结论　血清 MMP-9水平增高与粥样斑块破裂相关 ,可作为判断粥样斑块不稳定的血清学指标     

阿托伐他汀对急性冠状动脉综合征患者血清MMP-9及TIMP-1水平的影响

目的 :测定急性冠状动脉综合征 (ACS)患者经阿托伐他汀治疗前后血清明胶酶B(MMP 9)、基质金属蛋白酶组织抑制因子 1 (TIMP 1 )水平 ,探讨两者水平与粥样斑块破裂的关系及他汀类调脂药物稳定斑块的可能机制。方法 :选择稳定型心绞痛 (SAP)患者 3 0例 ,ACS患者 5 4例 ,并选择 3 0例健康人作为对照。随机将ACS患者分成阿托伐他汀治疗组 ( 3 0例 )及常规治疗组 ( 2 4例 ) ,比较各组患者血清MMP 9,TIMP 1水平变化。结果 :SAP、ACS、健康对照组三组之间MMP、TIMP 1水平比较差异有统计学意义 ,阿托伐他汀治疗组与常规治疗组治疗后血清MMP 9、TIMP 1水平相比差异有统计学意义。结论 :血清MMP 9升高及TIMP 1降低与粥样斑块破裂明显相关。阿托伐他汀可降低ACS患者血清MMP 9水平 ,升高TIMP 1水平 ,从而起到稳定斑块的作用     

Association between serum matrix metalloproteinase-9 and poor prognosis in acute ischemic stroke patients: The role of dyslipidemia

Background and aimsWhether the prognostic value of matrix metalloproteinase-9 (MMP-9) is modified by patients' dyslipidemia status is unknown. The aim of present study was to evaluate the prognostic effect of MMP-9 among ischemic stroke patients stratified by dyslipidemia status.Methods and resultsMMP-9 levels were measured for 2977 acute ischemic stroke patients from 26 participating hospitals across China, and data of clinical outcomes within one year after ischemic stroke was collected. The primary outcome was a composite outcome of major disability and death at one year after stroke onset, and secondary outcomes were major disability, death, vascular events and recurrent stroke. The association between MMP-9 and primary outcome was appreciably modified by dyslipidemia status (P_interaction = 0.048). After multivariate adjustment, increased MMP-9 level was associated with increased risk of primary outcome at one year after ischemic stroke in the patients with dyslipidemia (odds ratio, 1.34; 95% confidence interval, 1.06–1.79), but not in those without dyslipidemia (odds ratio, 1.23; 95% confidence interval, 0.90–1.68). Increased MMP-9 was also significantly associated with major disability, death and vascular events in the patients with dyslipidemia but not in those without dyslipidemia (P for interaction < 0.05 for all).ConclusionIncreased MMP-9 was associated with poor prognosis within one-year after stroke only in patients with dyslipidemia, suggesting that the prognostic value of MMP-9 be modified by dyslipidemia status of ischemic stroke patients. Further prospective study from other populations and randomized clinical trials are needed to verify our findings and clarify the potential mechanisms.     

Short-term effects of atorvastatin on C-reactive protein.

AIM: To study the short-term effect of atorvastatin on C-reactive protein (CRP) in patients with or at risk for coronary heart disease. METHODS AND RESULTS: One hundred and fifty-five randomly selected patients from the SWiss Intervention Trial for lowering CHolesterol (SWITCH) were assessed for high sensitivity CRP, total cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides at baseline, and after 1 and 3 months of treatment with atorvastatin at various doses to reach pre-defined lipid target values. The median decrease of cholesterol was 28% after 1 month and 35% after 3 months. LDL-cholesterol was decreased by 37% and 45%, HDL-cholesterol was increased by 7% and 8%, respectively. Patients with a low CRP baseline concentration (lowest quartile <1.34 mg. l(-1)) displayed no significant change, whereas patients in the other quartiles showed a significant decrease, of 22% to 40% (P -value <0.05 to <0.001) at 1 month and of 32% to 36% after 3 months compared to baseline. The decrease in CRP lowering was thus fully established by 1 month and this response was independent of lipid and lipoprotein changes as well as atorvastatin doses. CONCLUSION: Atorvastatin significantly decreases CRP concentrations after 4 weeks of therapy. These results may be important with respect to the early benefit of statin therapy.     

The Value of PAPP-A and MMP-9 in the Diagnosis and Outcome of ACS Patients

Objectives To investigate the value of pregnancy-associated plasma protein-A （ PAPP-A ） and matrix metallo proteinase-9 （MMP-9） in the diagnosis and outcomes evaluation of acute coronary syndrome （ACS） patient. Methods 100 ACS patients were divided into UAP group （ 64 cases ） and AMI group （ 36 cases）, and 50 healthy cases served as control group. The levels of PAPP-A, MMP-9, Hs-CRP, CK-MB and cTnI were obtained. The ACS patients with normal CK-MB and cTnI concentration were followed up. During 6 months, the total rates of major cardiovascular events （MACE） were recorded. Results Compared to control group, the PAPP-A, MMP-9, Hs-CRP, CK-MB, cTnI levels of ACS patients were significantly increased （ P 〈 0.01 ）, but the levels of PAPP-A, MMP-9 did not correlate well with CK-MB and cTnI. The ACS patients with normal CK-MB and cTnI concentration were followed up 6 months, the levels of PAPP-A, MMP-9 were significantly associated with the MACE （ P 〈 0.01 ）. Conclusions The levels of PAPP-A, MMP-9 of ACS patients were not associated with myocardial ischemic necrosis, but could serve as predictor of unstable atherosclerotic plaque, and as valuable index for prognosis monitoring in ACS patients.     

基质金属蛋白酶2、基质金属蛋白酶9与急性肺损伤关系的研究进展

急性肺损伤是由多种肺内外因素如严重创伤、感染、休克、脓毒症和大量输血等原因引起的弥漫性肺实质损伤.各种原因引起一系列炎症细胞在肺内聚集和活化,释放细胞因子、生长因子及其他炎症介质,引起基质金属蛋白酶(MMP)的合成和活化.MMP-2、MMP-9通过破坏基底膜、促进炎症过程中有关细胞的迁移以及细胞外基质重建,在急性肺损伤...     

C-reactive protein induces endothelial cell apoptosis and matrix metalloproteinase-9 production in human mononuclear cells: Implications for the destabilization of atherosclerotic plaque

C-reactive protein (CRP) has been suggested to directly induce the inflammatory response leading to the progression of atherosclerosis. However, recent in vitro studies raised the possibility that the effects of CRP are caused by biologically active contaminants such as sodium azide and endotoxin. In this study, we tested whether azide- and endotoxin-free CRP induces endothelial cell apoptosis and production of proinflammatory mediators. In human endothelial cells, CRP significantly inhibited cell proliferation and increased endothelial cell apoptosis evaluated by terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling and caspase-3 activity assay, which is reversed by a function-blocking antibody to Fc gamma RIIIB by 78%. Western blot analysis showed that CRP significantly attenuated flow-mediated activation of Akt, a key molecule for endothelial cell survival pathways. In human mononuclear cells, CRP-induced production of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and matrix metalloproteinase-9 (MMP-9) in a concentration-dependent manner. This CRP-induced MMP-9 production was significantly inhibited by function-blocking antibodies to TNF-alpha, IL-1 beta, and Fc gamma RIIA. These findings suggest that CRP itself induces endothelial cell apoptosis and production of proinflammatory mediators. Because endothelial cell apoptosis and MMP-9 production are critical for the destabilization of atherosclerotic plaque, this study may provide insight into a role of CRP in the development of plaque rupture.     

基质金属蛋白酶-9对大鼠动脉粥样硬化斑块内血管生成及斑块稳定性的影响

目的:研究基质金属蛋白酶-9（MMP-9）与动脉粥样硬化(AS)斑块内血管生成的关系及强力霉素干预的效果。方法: 将36只雄性Wistar大鼠随机分为对照组（A组,普通饮食喂养）、AS组（B组）和强力霉素干预组（C组）,B组和C组均给予高脂饮食＋维生素D3腹腔注射,C组同时给予强力霉素腹腔注射。采用酶法并以全自动生化分析仪测量血脂,双抗体夹心ABC-ELISA法检测血清MMP-9的水平。取主动脉切片行HE染色,观察斑块形态,计数易损斑块的数目。对内皮细胞标记物CD34行免疫组织化学染色法以检测斑块内新生血管密度。结果: B组和C组各项血脂的水平无明显差异,但均明显高于A组（P<0.05）。B组和C组血清MMP-9的水平明显高于A组（P<0.05）,B组又高于C组（P<0.05）。与B组比较,C组易损斑块数、CD34+面积/扫描面积(R)比均降低(P<0.01)。结论: 强力霉素能增强斑块稳定性,这种作用可能是通过降低MMP-9的水平进而减少了斑块内血管生成。     

急性冠状动脉综合征患者血浆白三烯B4和基质金属蛋白酶-9的水平变化及意义

目的:观察急性冠状动脉综合征(ACS)患者血浆白三烯B4(LTB4)与基质金属蛋白酶-9(MMP-9)水平的变化及其相关性,探讨其在ACS中可能的临床意义。方法:采用酶联免疫吸附法(ELISA)测定65例ACS患者以及20例健康对照人群(对照组)血浆LTB4和MMP-9的水平,以全自动生化分析仪测定血脂水平和C反应蛋白(CRP),并比较LTB4与MMP-9、血脂以及CRP的相关性。结果:ACS患者LTB4水平在急性心肌梗死(AMI)和不稳定型心绞痛(UAP)组分别为(112.77±22.59),(86.94±14.81)ng/L,显著高于对照组[(40.5±8.85)ng/L,P<0.01)],且AMI组高于UAP组(P<0.05)。LTB4与MMP-9的水平显著正相关(r=0.875,P<0.01),与CRP正相关(r=0.641,P<0.01),与TG正相关(r=0.469,P<0.01),与HDL-C负相关(r=-0.370,P<0.01)。结论:ACS患者血浆LTB4和MMP-9水平增高,LTB4可能与MMP-9以及CRP构成炎症网络并参与脂质代谢紊乱,导致动脉粥样斑块不稳定而成为ACS的危险信号。     

Matrix metalloproteinase-9: A deleterious link between hepatic ischemia-reperfusion and colorectal cancer

Despite the advent of improved surgical techniques and the development of cytotoxic chemotherapeutic agents useful for the treatment of colorectal cancer, the primary clinical challenge remains that of preventing and combating metastatic spread. Surgical resection is the best treatment for colorectal metastases isolated to the liver. However, in rodent models, the hepatic ischemia-reperfusion (I/R) applied during the surgery accelerates the outgrowth of implanted tumors. Among the adverse effects of I/R on cellular function, several studies have demonstrated an over expression of the matrix metalloproteinase-9 (MMP-9) in the ischemic liver. Since several studies showed high local levels of expression and activity of this proteolytic enzyme in the primary colorectal adenocarcinoma, the role of MMP-9 might be considered as a potential common mediator, favoring both growth of local tumor and the dissemination of colorectal carcinoma metastases.     

急性冠脉综合征支架置入后早期血清hsCRP、MMP-9、IL-18的变化及意义

目的观察急性冠脉综合征（ACS）患者冠脉内支架置入前后外周血血清基质金属蛋白酶-9（MMP-9）、IL-18、高敏C反应蛋白（hsCRP）的变化,探讨上述指标对预测支架置入后早期心血管不良事件的价值。方法选择48例ACS患者,根据术后随访结果分为有并发症组和无并发症组,分别于支架置入前、支架置入后24、48h及6个月检测血清hsCRP、MMP-9、IL-18水平。结果患者术后24、48h与术前比较,hsCRP、IL-18显著升高,MMP-9显著降低（P均〈0．05）;有、无并发症组术前上述指标无统计学差异（P均〉0．05）,有并发症组术后24、48h hsCRP、IL-18较术前明显升高,术后6个月血清hsCRP、IL-18较无并发症组显著升高（P均〈0．05）;两组术后24、48h MMP-9水平无统计学差异（P均〉0．05）。结论支架置入后早期并发症的发生与炎症反应有关,术后IL-18、hsCRP持续增高可能成为术后早期并发症的预测因子,术后加强抗炎治疗可预防早期并发症的发生。     

急性冠脉综合征患者外周血MMP-9及CRP的变化及其临床意义

目的观察急性冠脉综合征（ACS）患者外周血中基质金属蛋白酶-9（m atrix m etalloproteases-9,MMP-9）及C反应蛋白（CRP）的水平变化,探讨MMP-9、CRP与ACS发生的关系。方法选取ACS患者39例,采用双抗体夹心ELISA测定血清MMP-9的水平,CRP用免疫散射比浊法检测。结果ACS患者入院即刻血浆MMP-9、CRP水平均显著高于对照组[（66±16）vs（24±11）μg/L,P<0.01;（12.3±9.2）vs（3.5±2.0）mg/L,P<0.01]。ACS组内UA亚组与AM I亚组比较,MMP-9水平显著增高[（78±11）vs（50±14）μg/L,P<0.01],而CRP水平显著下降[（7.2±2.2）vs（18.7±10.7）mg/L,P<0.01]。ACS组患者中MMP-9和CRP水平无明显相关性。结论冠心病患者外周血MMP-9、CRP水平升高。ACS患者中MMP-9和CRP水平无明显相关性。     

Peripheral levels of matrix metalloproteinase-9, interleukin-6, and C-reactive protein are elevated in patients with acute coronary syndromes: correlations with serum troponin I

BACKGROUND: Acute coronary syndromes (ACS) are characterized by activation of systemic and local inflammatory mediators. The interrelation between these soluble inflammatory markers and their association with markers of myocardial necrosis have not been extensively studied. HYPOTHESIS: The study was undertaken to evaluate the association of the systemic levels of matrix metalloproteinase-9 (MMP-9) and the tissue inhibitor of metalloproteinase-1 (TIMP-1), with C-reactive protein (CRP), interleukin-6 (IL-6), and serum troponin-I in patients admitted with ACS. METHODS: Analysis of serum concentrations of the above inflammatory markers was performed in 53 patients with unstable angina (UA) and in 15 with non-ST-segment elevation myocardial infarction (NSTEMI) within 48 h of admission, and 34 patients with stable coronary artery disease. RESULTS: Compared with patients with stable angina, those with ACS had elevated admission levels of MMP-9 (p = 0.04), CRP (p < 0.001), and IL-6 (p = 0.001), but not TIMP-1 (p = 0.55). Compared with patients with UA, those with NSTEMI also had higher levels of IL-6 (p < 0.001), CRP (p = 0.002), and MMP-9 (p = 0.05). CONCLUSIONS: In patients with ACS, the admission levels of inflammatory mediators, including MMP-9, CRP, and IL-6 are significantly elevated, specifically in association with serum troponin I. Systemic and local markers of inflammatory activity may be directly associated with myocardial injury.     

血清基质金属蛋白酶9及高敏C反应蛋白与糖尿病肾病关系的探讨

目的探讨血清基质金属蛋白酶9(MMP-9)及高敏C反应蛋白(hsC-RP)与糖尿病肾病(DN)发生的相关性。方法根据尿白蛋白/肌酐比值(UAlb/Cr)将80例2型糖尿病患者分为单纯糖尿病组(DM,UAlb/Cr<30mg/g,52例)和糖尿病肾病组(DN,UAlb/Cr≥30mg/g,28例),测定患者的MMP-9及hsC-RP水平。结果DN组患者的MMP-9浓度为(341±155)μg/L,hsC-RP浓度为(4·9±3·7)mg/L,分别显著高于DM组的(210±150)μg/L及(2·6±2·8)mg/L(P均<0·01);MMP-9及hsC-RP升高均与UAlb/Cr呈正相关(MMP-9=0·59UAlb/Cr 216·90,C-RP=0·015UAlb/Cr 2·51)。结论MMP-9和C-RP可能与DN的发生相关。