间歇性低温刺激减少载脂蛋白E基因敲除小鼠动脉粥样硬化斑块内胶原含量的研究

目的：研究间歇性低温刺激对载脂蛋白E（ApoE-/-）基因敲除小鼠动脉粥样硬化斑块内胶原含量的影响。
　　方法：20只8周龄的雄性ApoE-/-小鼠被随机分为对照组和实验组,实验组小鼠每天8：00至12：00置于（4±1）° C环境中,其余时间和对照组小鼠一样处于（24±2）° C环境。饲养12周后,Masson染色了解小鼠主动脉根部动脉粥样硬化斑块内胶原情况,蛋白免疫印迹法（Western Blot）检测小鼠主动脉基质金属蛋白酶（MMPs）2、9及基质金属蛋白酶抑制剂1的表达情况。
　　结果：Masson染色见实验组小鼠主动脉根部斑块内胶原含量低于对照组,Western blot实验组小鼠主动脉MMP2、MMP9表达高于对照组,TIMP1表达低于对照组。
　　结论：间歇性低温刺激可能通过破坏MMPs/TIMPs之间的平衡,引起动脉粥样硬化斑块内胶原含量减少,造成易损斑块的形成,导致急性冠状动脉综合征的发生。     

基质金属蛋白酶在大鼠心肌梗死模型心室重塑中的作用

目的:研究心肌梗死(MI)后基质金属蛋白酶2,9(MMP2,9)和组织金属蛋白酶抑制酶1(TIMP1)的变化规律,以及在左心室重塑过程中的作用。方法:通过结扎SD大鼠冠状动脉前降支建立MI模型。另设空白对照组、手术对照组。取MI术后第1天,术后1、2、4周各组心肌组织,采用免疫组化法测定其胶原含量和Ⅰ/Ⅲ胶原比例,酶谱法测定MI后MMP2,9活性蛋白的表达规律,WesternBlotting进一步确定酶谱法中所消化条带蛋白的属性,逆转录聚合酶链反应法(RTPCR)测定MI后MMP2、9和TIMP1mRNA的变化规律。结果:SD大鼠心肌内胶原含量在MI后第2、4周增加(P<0.01),Ⅰ/Ⅲ胶原比例同时期下降(P<0.05),MMP2、9蛋白水平和mRNA水平在MI后活性增强、表达增加,TIMP1蛋白含量减少。结论:SD大鼠MI后心肌组织内MMP2、9mRNA转录增加,TIMP1mRNA转录减少,MMP2、9活性增高和蛋白含量增加,TIMP1蛋白表达减少,胶原含量增加,Ⅰ/Ⅲ胶原比例下降,是参与心室重塑机制的重要组成部分。     

基质金属蛋白酶与冠状动脉斑块稳定性相关研究

目的 :探讨基质金属蛋白酶 1(MMP 1)、基质金属蛋白酶抑制剂 1(TIMP 1)、TIMP 1/MMP 1与冠状动脉 (冠脉 )粥样硬化斑块稳定性的相关性。方法 :以冠脉血管内超声检出冠脉粥样硬化斑块的软硬特性 ,将急性冠脉综合征患者分为不稳定斑块组 (n =2 2 )和稳定斑块组 (n =12 )。测定两组间血浆MMP 1、TIMP 1浓度 ,并与冠脉血管内超声测定的斑块大小、斑块纤维帽厚度、脂核或无回声带大小、脂核或无回声带与斑块比及面积狭窄率进行相关性分析。结果 :在冠状静脉窦血和外周血中 ,不稳定斑块组MMP 1浓度明显大于稳定斑块组 (P <0 0 1) ,TIMP 1/MMP 1明显小于稳定斑块组 (P <0 0 0 1) ,有非常显著性差异。血浆MMP 1浓度与纤维帽厚度呈负相关 ,与脂核或无回声带面积、脂核与斑块比和面积狭窄率呈正相关 ,与斑块大小无关。TIMP 1/MMP 1与纤维帽厚度、面积狭窄率呈正相关 ,与脂核或无回声带面积、脂核与斑块比呈负相关。结论 :MMP 1和TIMP 1/MMP 1与冠脉斑块不稳定性呈密切相关 ,可望作为冠脉斑块不稳定性的参考指标。     

基质金属蛋白酶在类似人类2型糖尿病大鼠肾病中的研究

目的 动态研究基质金属蛋白酶－2（MMP－2）和其体内特异的抑制物－金属蛋白酶组织抑制剂－2（TIMP－2）在类似人类2型糖尿病大鼠肾组织的改变。方法 利用免疫组织化学观察Ⅳ型胶原在肾小球的表达,酶谱法测定肾皮质MMP－2的活性,蛋白印迹法检测肾皮质TIMP－2的含量,Northern Blot观察肾皮质MMP－2和TIMP－2的基因表达。结果 类似人类2型糖尿病大鼠肾小球Ⅳ型胶原成分表达增强,肾皮质MMP－2基因表达减弱（P＜0．01）;其活性进行性减少（P＜0．0001）,而TIMP－2基因表达（P＜0．01）及其含量逐渐增加（P＜0．01）。结论 类似人类2型糖尿病大鼠肾组织MMP－2活性进行性降低、TIMP－2含量增加,两者比例失衡为肾小球ECM成份沉积的重要原因之一,基质降解减弱也参与了2型糖尿病大鼠肾脏病变的发生和发展。     

高棕榈酸饮食对ApoE基因敲除小鼠动脉粥样硬化的影响

1目的：观察高棕榈酸饮食对载脂蛋白E（ApoE）基因敲除小鼠的血脂、血浆游离脂肪酸水平、动脉粥样硬化斑块面积、斑块中胶原含量和基质金属蛋白酶2表达的影响。方法：将20只6～8周龄雄性ApoE基因敲除小鼠随机分为对照组和高棕榈酸饮食组,每组10只。分别给予普通小鼠饲料和含5％棕榈酸的饮食,连续喂养12周。用比色法检测血脂和血浆游离脂肪酸水平;主动脉根部连续石蜡切片,Masson染色检测斑块内胶原含量,免疫组化法检测主动脉基质金属蛋白酶2的表达。结果：两组血脂水平无明显差异。与对照组相比,高棕榈酸饮食组血浆游离脂肪酸水平显著升高,主动脉斑块内胶原含量显著降低,主动脉基质金属蛋白酶2表达明显增加（P均〈0．05）。结论：高棕榈酸饮食能够升高血浆游离脂肪酸水平,降低斑块内胶原含量,从而降低动脉粥样硬化斑块稳定性,其机制可能与其上调基质金属蛋白酶2的表达有关。     

L-158809对2型糖尿病大鼠模型肾脏保护的机制探讨

目的：观察血管紧张素Ⅱ（ATⅡ）受体拮抗剂L－158809对2型糖尿病大鼠模型肾脏的保护作用,并探讨其作用机制。方法：2型糖尿病大鼠在L－158809治疗16周后,测定肾组织ATⅡ含量,利用组织学检查观察肾组织结构的改变,免疫组化观察基质金属蛋白酶2（MMP－2）及其金属蛋白酶2组织抑制剂（TIMP－2）在肾小球的表达,酶谱法测定肾皮质MMP－2的活性,Western印迹检测肾皮质TIMP－2的含量,结果：L－158809治疗使糖尿病大鼠血浆和肾皮质ATⅡ浓度进一步升高,肾小球基质增生明显减轻,肾小球MMP－2染色强度和肾皮质MMP－2的活性增强,但不能使肾小球TIMP－2染色及肾皮质TIMP－2含量降至正常。结论：L－158809对类似人类2糖尿病大鼠肾脏病变有保护作用,对肾脏细胞外基质沉积的改善部分是通过促进基质转化而实现的。     

MT1-MMP、MMP-2和TIMP-2基因在去卵巢大鼠成骨细胞中的表达

目的　通过观察去卵巢 (OVX)骨质疏松模型大鼠成骨细胞膜型基质金属蛋白酶 1(MT1 MMP)基因的表达 ,探讨绝经后骨质疏松的发病机制。　方法　对OVX大鼠与假手术大鼠进行骨密度和骨组织形态计量学测定。股骨远端行原位杂交检测骨组织MT1 MMP、MMP 2和TIMP 2mRNA表达 ,免疫组化检测骨组织MT1 MMP、MMP 2和TIMP 2蛋白质表达。　结果　OVX大鼠第 3、4腰椎骨密度 (0 14 4± 0 0 11) g cm2 、(0 14 3± 0 0 15 ) g cm2 较对照组 (0 15 8± 0 0 18)g cm2 、(0 16 2± 0 0 17) g cm2 明显减少 ,OVX组骨小梁面积 (9 5 8± 3 39) %、厚度 (40 85± 8 0 4 ) μm和数目 (2 30± 0 4 8)个 mm分别较对照组 (2 0 6 3± 4 8) %、(44 73± 6 8) μm、(4 6± 0 7)个 mm明显下降 ,OVX组骨小梁间隔 (5 85 8± 115 1) μm较对照组 (2 5 4 6± 4 8 0 ) μm明显增宽 ;成骨细胞MT1 MMPmRNA与蛋白质表达下调 ,而MMP 2和TIMP 2之间表达无差异。　结论　雌激素不足可使成骨细胞MT1 MMP基因表达减少 ,可能为绝经后骨质疏松的发病机制之一。     

心房颤动患者心房组织中明胶酶的基因表达及活性变化

目的　检测明胶酶及其内源性抑制剂金属蛋白酶组织抑制因子(TIMPs)和基质金属蛋白酶(MMPs)在心房颤动(房颤)患者心房组织中的表达和明胶酶活性的变化,探讨房颤患者心房结构重构的分子机制。方法　75例风湿性心脏瓣膜病(风心病)接受换瓣手术者分为三组,其中窦性心律组 34例,阵发性房颤组 11例,持续性房颤组 30例;于术中获取右心耳组织,分别采用半定量逆转录 聚合酶链反应技术和免疫印迹法测定MMP 2、MMP 9、TIMP 1、TIMP 2的mRNA含量和蛋白含量,酶谱法测定MMP 2、MMP 9的活性。结果　(1)与窦性心律组比较,MMP 2的mRNA水平在阵发性房颤组、持续性房颤组心房组织中均明显增加(P<0 01,P<0 001);各组患者MMP 9的mRNA水平相似。持续性房颤组MMP 2、MMP 9的蛋白表达水平较窦性心律组、阵发性房颤组均明显增加 (P<0 01)。阵发性房颤组MMP 2、MMP 9的蛋白表达水平较窦性心律组亦明显增加 (均为P<0 05 )。(2)与窦性心律组比较,持续性房颤组TIMP 1、TIMP 2的mRNA及蛋白表达水平均明显下调 (P<0 05~0 01)。(3)与窦性心律组比较,持续性房颤组、阵发性房颤组MMP 2、MMP 9的活性均明显增加(P<0 05~0 01),持续性房颤组的MMP 9活性较阵发性房颤组亦明显增加 (P<0 01 )。( 4 )MMP 2、MMP 9的mRNA及蛋白表达水平与左心房内     

光学相干断层成像技术评价动脉粥样硬化斑块

目的　应用光学相干断层成像（OCT）技术评价动脉粥样硬化斑块纤维帽厚度及其结构特征。方法　24只雄性新西兰大白兔,应用球囊拉伤加高脂饲养的方法制作动脉粥样硬化模型,动物随机分为两组：治疗组（n12）和对照组（n12）。对照组给予高脂饲料喂养,共22周;治疗组前10周给予高脂饲料喂养,后12周改为普通饲料喂养同时给予阿托伐他汀2　mg/（kg·d）。应用OCT评价血管管腔面积、管腔偏心指数、斑块纤维帽厚度及视频密度。22周处死动物后取靶血管行HE染色。结果　24只动物在第10周末OCT检查可见动脉粥样硬化斑块。第22周时治疗组管腔面积显著大于对照组（2.07±0.48　mm²比1.50±0.52　mm²,P0.016）,管腔偏心指数小于对照组（18.74%±9.28%比27.35%±7.21%,P0.025）。对照组斑块纤维帽厚度小于治疗组,但无统计学差异（70.00±26.08　μm比94.55±29.79　μm,P0.053）。分析OCT图像的视频密度显示,22周时对照组斑块纤维帽视频密度显著低于治疗组（49.7±7.5比59.4±4.3,P0.004）,相关性分析显示斑块纤维帽视频密度与细胞数量存在线性关系（R0.706,P0.001）。结论　OCT能精确评价动脉粥样硬化斑块纤维帽厚度变化,图像视频密度可用于反应斑块纤维帽结构特征。     

MMP-1、TIMP-1在病毒性心肌炎小鼠心肌胶原重构中的作用

目的探讨基质金属蛋白酶鄄1(MMP鄄1)、金属蛋白酶组织抑制因子鄄1(TIMP鄄1)在心肌炎小鼠心肌胶原重构中的作用。方法用VG染色和图像分析、原位杂交方法观察病毒性心肌炎小鼠及同龄的对照小鼠各时期心肌组织胶原改变及MMP鄄1mRNA、TIMP鄄1mRNA的表达。结果与对照组比较,感染后第14天心肌组织胶原增加不明显,感染后第28天心肌组织血管周围胶原面积(PVCA)显著增加(P<0.001),感染后第56天PVCA及心肌胶原容积分数(CVF)均显著增加(P<0.001)。感染后第7天心肌MMP鄄1mRNA呈现一过性表达;感染后第7天可见TIMP鄄1mRNA表达,第14～21天最为明显,此后减弱,直到第56天。结论TIMP鄄1mRNA表达上调可能在病毒性心肌炎心肌胶原重构中起着重要作用。     

Different expression of MMPs/TIMP-1 in human atherosclerotic lesions. Relation to plaque features and vascular bed

Background: Proteolytic imbalance might determine arterial remodeling and plaque destabilization in atherosclerotic vessels. The aim of this study was to examine differences in the patterns of metalloproteinases (MMPs) and MMP inhibitor (TIMP-1) expression in advanced human atheromas, both in relation to the plaque features and the vascular bed involved. Methods and results: Immunohistochemistry for MMP-1, -3, -9 and TIMP-1 as well as the collagen content were measured in vascular sections from patients undergoing peripheral revascularization (carotid n=11, femoral n=23) and aorto-coronary bypass surgery (mammary arteries n=20, as controls). Increased expression of all MMPs was detected in atherosclerotic as compared with control sections (P<0.01). Aneurismal plaques showed a significant increase of MMP-1 and-3 and a reduction in total collagen (P<0.05) in relation to occlusive lesions. Calcification areas in atherosclerotic plaques were consistently associated with increased TIMP-1 expression (P<0.01). Finally, MMP-9 expression was higher in occlusive lesions from carotid than femoral arteries (P<0.01). Conclusions: Aneurysm lesions expressed higher MMP-1 and-3 expression than occlusive plaques, and MMP-9 was mainly detected in carotid as compared with femoral arteries. TIMP-1 was associated with arterial calcification. These differences in the MMPs/TIMP-1 expression might determine the evolution of advanced atherosclerotic plaques and contribute to its vulnerability.     

普萘洛尔对大鼠动脉粥样硬化斑块内MMP-9及TIMP-1表达的影响

目的探讨普萘洛尔对大鼠动脉粥样硬化斑块内基质金属蛋白酶-9(MMP-9)及金属蛋白酶组织抑制剂-1(TIMP-1)表达的影响。方法30只Wistar大鼠经高脂、高维生素D、免疫损伤处理17周造成动脉粥样硬化模型,随机分为对照组和普萘洛尔组,每组15只。所有大鼠在继续高脂喂养基础上,普萘洛组予普萘洛尔5mg/(kg.d)灌胃;对照组予生理盐水1ml/d灌胃,一周后处死全部大鼠,取主动脉粥样硬化斑块用免疫组织化学方法检测动脉粥样硬化斑块内巨噬细胞浸润、MMP-9及TIMP-1表达。结果普萘洛尔组巨噬细胞浸润数目及MMP-9的表达较对照组明显减少(P0.01),TIMP-1表达明显增高(P0.05)。结论普萘洛尔减少大鼠动脉粥样硬化斑块处巨噬细胞浸润及MMP-9表达,增加TIMP-1表达,具有稳定动脉粥样硬化斑块作用。     

应用光学相干断层成像对老年与中青年颈动脉粥样硬化性斑块特征的分析

目的 应用光学相干断层成像(OCT)评价老年与中青年患者颈动脉粥样硬化性斑块特征的区别.方法 回顾性连续纳入2017年6月至2021年2月在东部战区总医院神经内科完成颈动脉OCT检查的颈动脉粥样硬化性狭窄患者86例,分别将年龄<60岁、年龄≥60岁患者分为中青年组(17例,占19.8％)和老年组(69例,占80.2％)...     

白藜芦醇对动脉粥样硬化兔心肌纤维化和基质金属蛋白酶2、组织型基质金属蛋白酶抑制剂2表达的影响

目的 观察白藜芦醇对动脉粥样硬化兔心肌间质胶原纤维变化和基质金属蛋白酶2及组织型基质金属蛋白酶抑制剂2表达水平的影响.方法 33只新西兰白兔随机分为对照组、模型组和白藜芦醇干预组.观察心肌间质胶原纤维的变化,测量心肌间质胶原容积分数.逆转录聚合酶链反应检测心肌组织基质金属蛋白酶2及组织型基质金属蛋白酶抑制剂2 mRNA水平.结果 与对照组相比,模型组胶原纤维明显增多、增粗、排列紊乱,呈不规则网状或粗块状沉积于心肌间质,胶原容积分数和基质金属蛋白酶2表达增多,组织型基质金属蛋白酶抑制剂2表达减少(P<0.01).白藜芦醇干预能显著减少上述指标的改变.结论 动脉粥样硬化进程中,存在着心肌纤维化、基质金属蛋白酶2表达增多和组织型基质金属蛋白酶抑制剂2表达减少等现象,白藜芦醇能减轻基质金属蛋白酶2/组织型基质金属蛋白酶抑制剂2表达的失衡,改善心肌纤维化.     

Local plasminogen activator inhibitor type 1 overexpression in rat carotid artery enhances thrombosis and endothelial regeneration while inhibiting intimal thickening

Elevated levels of plasminogen activator inhibitor type 1 (PAI-1) are found in advanced atherosclerotic plaque compared with normal vessel and may contribute to plaque progression and complications associated with plaque rupture. Increased expression of PAI-1 probably contributes to the thrombotic properties of advanced atherosclerotic plaque by impeding plasmin generation and degradation of fibrin. To test this hypothesis, we have deliberately created synthetic neointimas by seeding onto the denuded luminal surface of rat carotid arteries smooth muscle cells transduced with replication-defective retrovirus encoding rat PAI-1. This cell-based gene transfer method results in stable, long-term, and localized gene expression. PAI-1 overexpression increases mural thrombus accumulation at 4 days but decreases neointimal area by 30% and 25% at 1 week and 2 weeks, respectively. PAI-1 overexpression accelerates reendothelialization of injured arteries compared with control arteries at 1 week, 2 weeks, and 1 month. PAI-1 overexpression does not alter matrix accumulation at 1 week. Increased PAI-1 expression in the rat carotid artery enhances thrombosis and endothelial regeneration while inhibiting intimal thickening. These results suggest that PAI-1 could play a direct role in the development of advanced atherosclerotic plaque and in the repair of the diseased vessel after fibrous cap disruption.     

睾酮对雄兔氧化炎性系统和动脉粥样硬化斑块稳定性的影响

目的:探讨睾酮对雄兔血丙二醛(MDA)、超氧化物歧化酶(SOD)、高敏C反应蛋白(hs-CRP)、基质金属蛋白酶-9(MMP-9)、血红素氧化酶-1(HO-1)和动脉粥样硬化斑块稳定性的影响。方法:将66只雄性新西兰纯种兔随机分为4组,其中正常对照组10只(A组),喂以普通饲料;假去势+球囊损伤颈动脉组16只(B组),去势+球囊损伤颈动脉+生理剂量睾酮(6 mg/kg/2周)肌注组16只(C组)、去势+球囊损伤颈动脉+生理盐水肌注组24只(D组)均喂以高脂饲料。在实验第8周随机抽取处死部分动物,观察颈动脉病变的形态特征,抽血测睾酮、MDA、SOD、hs-CRP、MMP-9及HO-1水平。结果:D组兔血睾酮水平显著降低;B,C组较D组兔血MDA、hs-CRP及MMP-9水平显著降低,SOD、HO-1水平显著升高;且B,C组较D组兔动脉粥样斑块的面积和内-中膜厚度(IMT)显著减小,斑块纤维帽增厚、胶原含量明显增加。结论:生理剂量睾酮可以影响雄兔血MDA、SOD、hs-CRP、MMP-9及HO-1水平,并能调节动脉粥样硬化斑块进展与斑块的稳定性。     

Relation of arterial geometry to luminal narrowing and histologic markers for plaque vulnerability: the remodeling paradox

Objective. To relate local arterial geometry with markers that are thought to be related to plaque rupture.Background. Plaque rupture often occurs at sites with minor luminal stenosis and has retrospectively been characterized by colocalization of inflammatory cells. Recent studies have demonstrated that luminal narrowing is related with the mode of atherosclerotic arterial remodeling.Methods. We obtained 1,521 cross section slices at regular intervals from 50 atherosclerotic femoral arteries. Per artery, the slices with the largest and smallest lumen area, vessel area and plaque area were selected for staining on the presence of macrophages (CD68), T-lymphocytes (CD45RO), smooth muscle cells (alpha-actin) and collagen.Results. Inflammation of the cap or shoulder of the plaque was observed in 33% of all cross sections. Significantly more CD68 and CD45RO positive cells, more atheroma, less collagen and less alpha-actin positive staining was observed in cross sections with the largest plaque area and largest vessel area vs. cross sections with the smallest plaque area and smallest vessel area, respectively. No difference in the number of inflammatory cells was observed between cross sections with the largest and smallest lumen area.Conclusion. Intraindividually, pathohistologic markers previously reported to be related to plaque vulnerability were associated with a larger plaque area and vessel area. In addition, inflammation of the cap and shoulder of the plaque was a common finding in the atherosclerotic femoral artery.     

糖尿病患者动脉粥样硬化斑块内基质金属蛋白酶2和9与斑块稳定的关系

目的　比较糖尿病患者与非糖尿病组患者动脉粥样硬化斑块内基质金属蛋白酶 2和基质金属蛋白酶 9表达的差异 ,初步探索基质金属蛋白酶 2和基质金属蛋白酶 9与糖尿病动脉粥样硬化斑块稳定的关系。方法　从2 3例糖尿病足截肢和 17例尸检下肢动脉标本中选取晚期动脉粥样硬化病变的组织块共 12 6块 ,分为糖尿病组 (74块 )和非糖尿病组 (5 2块 ) ,从中随机选取各 4 0个组织块 ,运用免疫组织化学染色法检测基质金属蛋白酶 2和 9在两组粥样硬化斑块中的表达。结果　糖尿病组抗基质金属蛋白酶 2、抗基质金属蛋白酶 9免疫沉积物主要集中在斑块核心周围 ,特别是在斑块的肩部和纤维帽。糖尿病组动脉斑块内抗基质金属蛋白酶 2免疫沉积物表达显著高于非糖尿病组 (免疫沉淀物积分光密度值分别为 6 90 14± 14 4 5 9和 5 70 0 4± 16 171,阳性面积百分比分别为 13.0 %± 2 .7%和 11.1%± 3.3% ) ;糖尿病组斑块内基质金属蛋白酶 9表达也显著高于非糖尿病组 (免疫沉淀物积分光密度值分别为 10 2 4 85± 2 0 4 31和 75 2 80± 1310 6 ,阳性面积百分比分别为 18.4 %± 3.6 %和 13.7%± 2 .3% )。结论　基质金属蛋白酶 2和 9在糖尿病组动脉粥样硬化斑块中的表达显著高于非糖尿病组。基质金属蛋白酶 2和 9在糖尿病动脉中表达增     

Plasma MMP-2-TIMP-2 complex levels measured during follow-up predict a risk of relapse in patients with malignant lymphoma

Objectives:  Circulating gelatinases and their tissue inhibitors measured at diagnosis have been shown to exhibit prognostic relevance in several solid tumours. The clinical data concerning their role in follow-up of cancer are still very preliminary. The aim of this study was to find out whether the concentrations of these circulating markers could be used as follow-up markers predicting the risk of lymphoma relapse.
Methods:  Here, we investigated these circulating molecules in a large ( n  = 126) follow-up material of lymphoma patients and in healthy controls ( n  = 44). The plasma samples of patients with Hodgkin's lymphoma ( n  = 31), non-Hodgkin's lymphoma ( n  = 95), and healthy controls were analysed by enzyme-linked immunosorbent assay for matrix metalloproteinase-9 (MMP-9), proMMP-2, matrix metalloproteinase-2-tissue inhibitor of metalloproteinase-2 (MMP-2-TIMP-2) complex, TIMP-1, and TIMP-2.
Results:  The patients with the highest plasma levels of MMP-2-TIMP-2 complex had a 3-fold risk of relapse when compared to the patients with lower levels ( P  = 0.036). Plasma levels of proMMP-2 and MMP-2-TIMP-2 complex as well as the proMMP-2/TIMP-2 ratio were significantly higher in patients with active lymphoma and those in remission when compared to healthy controls. On the contrary, the values of TIMP-2 were significantly lower in lymphoma patients than in controls.
Conclusions:  This study shows that lymphoma patients with the highest levels of MMP-2-TIMP-2 complex are at a marked risk of relapse. Moreover, plasma levels of MMP-2-TIMP-2 complex, proMMP-2, TIMP-2, and proMMP-2/TIMP-2 ratio are at abnormal level in patients with newly diagnosed lymphoma and those in remission when compared to healthy controls. They remain abnormal even after successful lymphoma treatments.