Pleiotrophin的表达及其在血清水平与结肠癌的关系

目的：探讨pleiotrophin（PTN）的表达及其血清水平与结肠癌的关系。 方法：应用real time-PCR、Western blot方法检测46例结直肠癌组织及其对应癌旁组织中PTN mRNA及蛋白表达水平;ELISA方法检测76例结直肠癌患者和58例健康体检者血液样本中的PTN表达水平。 结果：PTN mRNA在结直肠癌组织中表达量以及PTN蛋白的阳性表达率均明显高于癌旁正常组织,差异均有统计学意义（均P<0.05）;无论是PTN mRNA表达水平还是蛋白阳性率均与患者年龄、肿瘤组织类型无关（均P>0.05）,而与肿瘤的分化程度呈负向关系、与TNM分期呈正向关系（均P<0.05）。结直肠癌患者血清PTN水平明显高于正常人群（P<0.05）。 结论：PTN在结直肠癌组织中表达增高;血清PTN水平检测可作为诊断结直肠癌参考指标之一。

     

中电导钙激动钾离子通道在原发性肝癌中的表达及其意义

目的：探讨中电导钙激动钾离子通道（SK4）在原发性肝细胞癌（HCC）中的表达情况及意义。 方法：收集46例HCC患者手术标本的HCC组织与癌旁组织。用免疫组化法检测两种组织中SK4与血管内皮细胞生长因子（VEGF）在的表达,分析HCC组织中SK4与VEGF表达的相关性;用real-time PCR法检测两种组织中SK4 mRNA的表达,并分析SK4 mRNA表达与HCC临床病理因素的关系。用Western blot法检测两种组织中SK4蛋白的表达。 结果：免疫组化结果显示,肝癌组织中SK4和VEGF的阳性表达率均明显高于癌旁组织（均P<0.05）,且在HCC组织中SK4和VEGF阳性表达呈正相关（r=0.364,P<0.05）;real-time PCR结果显示,HCC组织中SK4 mRNA表达水平较癌旁组织明显上调（P<0.05）,且SK4 mRNA的高表达与肿瘤低分化及门静脉癌栓有关（均P<0.05）;Western blot结果显示,SK4蛋白在HCC细胞膜的表达明显高于癌旁肝细胞,但两者胞质SK4水平无明显差异。 结论：SK4在HCC组织中表达增高,其可能通过上调VEGF的表达等途径促进HCC细胞的侵袭转移。

     

自噬抑制剂3-甲基腺嘌呤对结直肠腺癌细胞生长与Notch1蛋白表的影响

目的：探讨自噬抑制剂3-甲基腺嘌呤（3-MA）对人大肠癌SW480细胞生长与Notch1蛋白表达的影响。方法：将3-MA（5 mmol/L）作用于SW480细胞24 h后（以培养相同时间无处理的SW480细胞为对照）,分别免疫组化和Western blot法检测细胞Notch1蛋白的表达,用CCK-8法和Annexin/PI双染法检测细胞增殖与凋亡。结果：免疫组化与Western blot结果均显示,3-MA作用后,SW480细胞Notch1蛋白的表达明显下调（均P<0.05）;增殖与凋亡检测结果显示,3-MA作用后,SW480细胞增殖率明显降低,而凋亡率明显增加（均P<0.05）。结论： 3-MA能抑制结直肠癌细胞的增殖并促进其凋亡,该作用可能与3-MA抑制Notch1蛋白表达从而改变细胞自噬水平有关。

     

弹力蛋白酶加压灌注建立腹主动脉瘤大鼠模型方法的改进

目的：建立成功率高、符合人腹主动脉瘤（AAA）病理生理特点的大鼠AAA模型。方法：将20只SD大鼠随机均分为模型组和对照组,模型组通过左髂总动脉插管,行肾下腹主动脉节段猪胰弹力蛋白酶加压灌注（期间行一系列方法上的改进）,对照组以同样的方式接受生理盐水灌注。于术前、术后7,14 d通过彩色超声诊断仪检测两组灌注段腹主动脉尺寸,并于术后14 d取灌注段腹主动脉标本行弹力纤维染色。结果：术后7,14 d超声检测显示,对照组灌注段腹主动脉大小与术前比较无明显变化,模型组灌注段腹主动脉明显增大,模型成功率100%;术后14 d,模型组大鼠灌注段腹主动脉横截面积为术前的（5.17±0.61）倍,而对照组为（1.03±0.09）倍,两组差异有统计学意义（P<0.001）。弹力纤维染色显示,模型组血管中层弹力组织明显破坏,动脉壁弹性纤维相对含量明显低于对照组（P<0.001）。结论：通过改进方法,建立了成功率高,病理特征典型的大鼠AAA模型,为开展AAA的基础研究提供了良好稳定的实验模型。

     

内质网应激相关蛋白CHOP/GADD153在结肠癌组织中的表达及意义

目的：探讨结肠癌组织内质网应激相关蛋白CHOP/GADD153的表达,并分析其与临床病理特征的关系。方法： 选择82例结肠癌患者的结肠癌组织与相应的癌旁正常结肠组织（距癌组织>5 cm）制作蜡块后构建组织芯片,分别用免疫组化法及Western blot法检测CHOP/GADD153蛋白的表达,并分析其表达与患者临床病理特征分关系。结果：免疫组化与Western blot结果均显示,结肠癌组织CHOP/GADD153蛋白的表达水平明显癌旁正常结肠组织（P<0.05）;与临床病理特征的关系分析显示,结肠癌组织中CHOP/GADD153蛋白的表达水平随结肠癌组织分化程度的降低而增强（P<0.05）,而与患者的年龄、性别、肿瘤的大小、肿瘤的浸润深度和淋巴结转移等因素无关（均P>0.05）。结论：结肠癌组织中CHOP/GADD153蛋白的表达增高,并与结肠癌织的分化程度密切相关,提示内质网应激可能参与了肿瘤分化的调控。

     

兔腹主动脉瘤模型的建立

目的：探讨一种简便、成功率高的兔腹主动脉瘤（AAA）模型建立的方法。
方法:健康雄性新西兰大白兔20只，随机分为实验组和对照组（各10只），实验组应用CaCl2浸润法建模，对照组应用生理盐水浸润法。6周后观察两组动物腹主动脉扩张率、大体形态学及显微病理改变。
结果:实验组兔腹主动脉直径扩张至（124.12±8.11）%，与对照组相比差异有统计学意义（P＜0.01）。实验组腹主动脉的病理改变为中膜弹性纤维组织严重破坏，平滑肌细胞减少。
结论:CaCl2溶液浸润法制作兔AAA模型简单可行，为AAA的实验性治疗研究提供一种合适的造模方法。

     

β-微管蛋白的表达对胃癌根治术后辅助化疗的影响及其与预后的关系

目的：探讨胃癌患者胃癌组织中β-微管蛋白表达水平对胃癌根治术后紫杉醇化疗效果的影响。方法：选择接受胃癌根治术并术后进行紫杉醇辅助化疗的332例胃癌患者的组织样本,采用 RT-PCR法检测β-微管蛋白的mRNA表达水平,分析患者临床特征与β-微管蛋白mRNA表达的关系;Kaplan-Meier法比较β-微管蛋白高、低表达组生存时间的差异。结果：β-微管蛋白的mRNA表达水平与患者年龄、性别、肿瘤部位和肿瘤大小均无明显关系（均P>0.05）,而与分化程度、TNM分期、淋巴结转移和远处转移有关（均P<0.05）;β-微管蛋白的mRNA高表达组患者的术后生存时间比低表达组患者术后生存时间短,差异有统计学意义（P<0.05）。结论：胃癌组织中的β-微管蛋白表达水平与胃癌根治术及术后紫杉醇辅助化疗患者的远期生存率有密切关系,可作为患者预后的判断指标。

     

ADAM23|αvβ3在大肠癌中的表达与大肠癌肝转移的关系

目的：探讨ADAM23,αvβ3在大肠癌中的表达及其与肝转移等临床病理因素的关系。方法：应用免疫组化和RT-PCR方法检测53例大肠癌及其癌旁组织及20例良性病变组织中ADAM23,αvβ3的表达情况,并分析两者的蛋白表达与临床病理因素的关系。结果：大肠癌组织中ADAM23蛋白与mRNA阳性表达率明显低于癌旁组织与良性病变组织（均P<0.05）,而αvβ3蛋白与mRNA阳性表达率明显高于癌旁组织与良性病变组织（均P<0.05）。大肠癌组织中ADAM23和αvβ3蛋白的表达呈负相关（χ2=10.3390;r=-0.637,P<0.01）。ADAM23和αvβ3的蛋白表达与患者的性别,年龄及分化程度无关（均P>0.05）,而与临床分期,淋巴转移及肝转移有关,此外ADAM23蛋白的表达还与大肠癌浸润深度有关（均P<0.05）。结论：大肠癌中ADAM23呈低表达,αvβ3呈高表达,两者可能与大肠癌的肝转移等不良临床转归有关。

     

SELENBP1在结直肠癌中的表达及其与肿瘤分化的关系

目的：通过蛋白质组学技术筛选出结直肠癌（CRC）组织中差异表达最显著的蛋白，并探讨其与CRC疾病特征的关系。方法：收集83例CRC患者手术标本，包括患者的CRC组织，正常大肠黏膜组织，转移的淋巴结以及部分患者同时长有的大肠良性息肉。用二维差异凝胶电泳（2D DIGE）及基质辅助激光解析飞行时间质谱（MALDI-TOF-MS）对新鲜的CRC与正常黏膜组织以行蛋白质组学分析。找出兴趣蛋白后，用Western blot法在新鲜的CRC与正常黏膜组织，以及不同的CRC细胞株中验证；用免疫组化检测石蜡包埋的CRC、正常黏膜、良性息肉和转移淋巴结组织中该蛋白的表达。用Western blot法检测CRC细胞株在丁酸钠（NaB）诱导分化后该蛋白的表达改变。结果：2D-DIGE分析和MALDI-TOF-MS鉴定结果显示，CRC组织中硒结合蛋白1（SELENBP1）表达丰度比正常黏膜组织明显降低2.54倍（P<0.01）。Western blot示，CRC组织中SELENBP1的表达水平明显低于其配对的正常黏膜组织[（0.76±0.37） vs. (1.46±0.56）]（P<0.001），SELENBP1的表达在CRC细胞株中普遍降低。免疫组化示，SELENBP1的表达评分在CRC组织与正常黏膜组织中分别为1.25±0.78和2.02±0.77，组间差异有统计学意义（P<0.001）；在高、中、低分化的CRC组织中分别为1.75±0.53，1.29±0.41，0.89±0.49，组间差异有统计学意义（P<0.05）；在不同分期的CRC组织间、良性息肉与正常黏膜间、转移淋巴结与其配对的原发癌间，差异均无统计学意义（均P>0.05）。各CRC细胞株经NaB分化诱导后，SELENBP1表达均明显增高（均P<0.05）。结论：CRC组织SELENBP1表达降低，SELENBP1表达降低与CRC低分化程度有关，但与疾病进展及淋巴结转移无关。

     

血管平滑肌细胞凋亡在腹主动脉瘤发病中的作用

目的：探讨腹主动脉瘤（AAA）中膜血管平滑肌细胞（VSMC）密度降低的机制。方法：选取人体肾下AAA及正常腹主动脉组织（NA）标本,采用免疫组化及原位末端DNA标记技术,测定中膜VSMC,凋亡细胞及其相关蛋白,计算机图像分析并计算VSMC密度及凋亡指数。结果：与NA相比,AAA中膜VSMC密度降低,VSMC凋亡指数及其相关蛋白P53,P21明显增加,而bcl-2无显变化。结论：VSMC凋亡在细胞水平参与腹主动脉结构损伤与重构,促进AAA形成。     

u-PA和明胶酶A、B蛋白在人腹主动脉瘤组织中表达的研究

目的 探讨尿激酶型纤溶酶原活化物(u-PA)和明胶酶A、B在腹主动脉瘤(AAA)组织中蛋白的表达和产生的来源。方法 用u-PA和明胶酶A(MMP-2)、明胶酶B(MMP-9)的单克隆抗体,以免疫组织化学SABC方法在10例AAA组织和10例正常腹主动脉组织的切片上控测u-PA和MMP-2、MMP-9抗原(蛋白)。结果 u-PA和MMP-9蛋白在AAA组织中主要浸润于中层和外膜巨噬细胞表达,在正常腹主动脉组织中无表达,MMP-2蛋白在AAA组织中主要由中层平滑肌细胞表达,在正常腹主动脉组织中无表达。结论 由巨噬细胞产生的u-PA直接激活,并调节MMP-2和MMP-9的活性,在AAA的形成、扩张和破裂中起着关键性的作用。     

基质金属蛋白酶及抑制因子与腹主动脉瘤临床病理特点的相关性研究

目的：研究基质金属酶（MMP）-2、MMP-9及抑制因子TIMP-1在腹主动脉瘤中的表达及与临床病理特征之间的关系。方法：应用免疫组化PV-9000通用型二步法对70例腹主动脉瘤和15例正常腹主动脉标本中的MMP-2、MMP-9及TIMP-1表达进行检测。结果：腹主动脉瘤组织中MMP-2和MMP-9蛋白表达阳性率明显高于正常腹主动脉组织,TIMP-1蛋白表达阳性率和正常腹主动脉没有统计学差异,（X^2=0.103,P=0.991）;MMP-2蛋白的表达与腹主动脉瘤的直径呈负相关（X^2=13.785,P=0.032）,MMP-9蛋白的表达与患者临床症状,腹主动脉瘤直径、破裂有相关性,（P〈0.05）,TIMP-1蛋白表达阳性率与临床病理特征无相关性（X^2=0.103,P=0.991）。结论：腹主动脉瘤组织中MMP高表达和TIMP的相对弱表达在腹主动脉瘤发生、发展过程中起重要作用,MMP-9可以预测腹主动脉瘤的自然病程从而作为腹主动脉瘤手术治疗的指征之一。     

Mechanism of inhibition of matrix metalloproteinase-2 expression by doxycycline in human aortic smooth muscle cells

Degradation of the extracellular matrix components elastin and collagen has been implicated in vascular diseases, including abdominal aortic aneurysm (AAA) and atherosclerotic plaque rupture. Increased expression of matrix metalloproteinases (MMPs) is involved in these disease processes. Our previous studies have demonstrated that MMP-2 derived from mesenchymal cells is required for aneurysm development in a murine model. Doxycycline is a nonspecific inhibitor of MMPs. In the present study, the mechanisms of the inhibitory effects of doxycycline on MMP-2 expression from cultured human aortic smooth muscle cells (SMCs) and human aortic aneurysm tissue explants were studied. Doxycycline inhibited MMP-2 expression from cultured SMCs in a concentration-dependent manner (5-40 microg/mL; inhibitory concentration of 50%, 6.5 microg/mL). At normal therapeutic serum concentration (5 microg/mL) doxycycline significantly reduced MMP-2 production from SMCs (37%; P <.05), which were stimulated with conditioned media from macrophage or lymphocyte co-culture simulating the inflammatory milieu of AAA tissue. This correlated with a decrease in MMP-2 mRNA half-life, from 49 hours to 28 hours, which suggests that doxycycline inhibits SMC MMP-2 production in part by reducing MMP-2 mRNA stability. When AAA tissue was cultured for 10 days with doxycycline at concentrations of 2.5 to 40 microg/mL, the media exhibited a concentration-dependent decrease in both active and latent forms of MMP-2 and MMP-9. Doxycycline at a concentration of 5 microg/mL reduced active and latent MMP-2 secreted from cultured AAA tissue by 50% and 30%, respectively (P <.05). These study findings demonstrate that doxycycline at standard therapeutic serum concentrations inhibits MMP-2 expression from cultured human aortic SMCs and AAA tissue explants. Inasmuch as MMP activity contributes to extracellular matrix degradation in AAAs and atherosclerotic plaque, doxycycline may have potential value in treating these diseases.     

A 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor,cerivastatin, suppresses production of matrix metalloproteinase-9 in human abdominal aortic aneurysm wall

AIM: Abdominal aortic aneurysm (AAA) is a common vascular degenerative disease. AAA wall contains inflammatory cells that produce matrix metalloproteinases (MMPs) that probably contribute to elastolysis and remodeling of the aneurysm. 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have been shown to reduce the expression of various molecules (including MMPs) independently of their cholesterol-lowering effect. The aims of this study are to investigate whether statins could modulate the biology of AAA wall and have a potential therapeutic value against AAAs. METHODS: We performed immunohistochemical analysis, evaluated MMP-9 production in the aortic wall from patients with infrarenal AAA (n = 10) and control patients with aortoiliac occlusive disease (n = 8), and examined the effect of cerivastatin on MMP-9 production in the AAA wall with organ culture. RESULTS: Neutrophils and macrophages were the cellular sources of MMP-9 in the AAA wall. The tissue concentrations of both total and active MMP-9 were significantly higher in tissues from AAA walls than in control aortic walls. Cerivastatin (0.001 to 0.1 micromol/L) significantly reduced the tissue levels of both total and active MMP-9 in a concentration-dependent manner (P <.001), and the production of tissue inhibitor of MMP-1 was unaffected. Cerivastatin neither reduced the number of infiltrating neutrophils and macrophages nor enhanced apoptosis of those cells, as evaluated with terminal transferase-mediated deoxyurisine triphosphate nick end labeling. CONCLUSION: These results suggest that cerivastatin can directly modulate the biology of the AAA wall and suppress MMP-9 production in the AAA wall by inhibiting the activation of neutrophils and macrophages, indicating that statin therapy could be useful for the prevention or treatment of AAA.     

MF-tricyclic inhibits growth of experimental abdominal aortic aneurysms

BACKGROUND: Experimental abdominal aortic aneurysm (AAA) development can be pharmacologically suppressed by inhibiting matrix metalloproteinase-9 (MMP-9). Cyclooxygenase-2 (COX-2) inhibitors are potent anti-inflammatory agents that have been demonstrated to inhibit experimental aneurysm development. We hypothesized that treatment with MF-tricyclic, a selective COX-2 inhibitor, incorporated into rodent chow would inhibit aneurysm development in a rat AAA model. METHODS: Twelve male Sprague Dawley rats underwent induction of experimental AAA using intra-aortic porcine elastase infusion. Six rats received control feed, and six received MF-tricyclic rodent chow for a period of 14 days. Aortic diameters were measured pre- and postinfusion as well as at harvest. Aortic tissue samples were evaluated by real-time polymerase chain reaction (RT-PCR) for MMP-9, by immunohistochemistry for elastin. RESULTS: Elastase infusion produced AAA in all untreated rats. At 14 days MF-tricyclic-treated rats had significantly reduced aortic diameter (1.9 +/- 0.1 mm versus 2.4 +/- 0.0 mm, P = 0.00001). Percent increase in aortic diameter was also significantly less in animals receiving MF-tricyclic (65.7 +/- 8.5% versus 132.3 +/- 7.3%, P = 0.0001). RT-PCR demonstrated a decrease in the mean expression of MMP-9 in the treated animals (0.414 ng of RNA versus 1.114 ng of RNA) (P = 0.07). Sections stained for elastin demonstrated preserved elastin integrity in MF-tricyclic treated aortas. CONCLUSIONS: COX-2 inhibition helps to retard the growth of experimental AAAs possibly through inhibition of MMP-9. Experimentally treated animals demonstrated smaller aortic diameters and lower levels of tissue MMP-9 when compared to untreated animals. Selective COX-2 inhibition may offer an additional method to pharmacologically inhibit AAAs.     

基质金属蛋白酶在腹主动脉瘤组织中的表达

目的探查基质金属蛋白酶类（MMPs）在腹主动脉瘤（AAA）组织中产生的源泉。方法采用间质胶原酶（MMP-1）和明胶酶以MMP-9）的mRNA探针在20例AAA组织及4例正常人腹主动脉组织的切片上行原位杂交实验结果MMP-1及MMP-9在巨噬细胞、平滑肌细胞和淋巴细胞均有表达,其中巨噬细胞的MMPs表达强烈。结论MMPs在AAA的形成和扩张中发挥重要作用,炎性细胞是产生MMPS的主要源泉,并影响问质细胞的MMPS表达。     

Matrix metalloproteinase expressions in arteriosclerotic aneurysmal disease

Medial degeneration of extracellular matrix (ECM) proteins in the wall of abdominal aortas results in smooth muscle cell destruction, a loss of architectural integrity, and abdominal aortic aneurysm (AAA) formation. It has been theorized that an imbalance between proteinases and their naturally occurring inhibitors is the cause of these observed histologic abnormalities. Therefore, the purpose of this investigation was to determine if differences in the matrix metalloproteinase (MMP) -2 and -9, tissue inhibitor of metalloproteinase-1 (TIMP-1), tissue-type plasminogen activator (tPA), and urokinase-type plasminogen activator (uPA) protein and activity levels existed between infrarenal AAA and normal abdominal aortic tissue specimens. Between November 1995 and January 1997, 10 patients undergoing elective infrarenal AAA repair had a portion of their aneurysm walls snap frozen in liquid nitrogen and processed for subsequent western blot or zymographic analysis. Tissue specimens from 6 normal abdominal aortas obtained from fresh cadaver specimens were similarly processed and served as controls. Protein levels for MMP-2, MMP-9, TIMP-1, uPA, and tPA were analyzed by western blotting. The degree of MMP-2 and MMP-9 gelatinolytic activity was analyzed by zymography. Detection and immunolocalization for MMP-2, MMP-9 and CD68 was performed on tissue sections of AAA and normal infrarenal abdominal aortas fixed in 10% formalin. MMP-9 and tPA protein levels were increased in AAAs compared to controls by western blotting. However, uPA levels were slightly increased in controls. No differences in TIMP-1 protein levels were identified. Similarly, zymography demonstrated increased MMP-2 and MMP-9 gelatinolytic activity in AAAs compared to controls (p < or = 0.05). CD68-positive cells (macrophages) in the adventitia and media demonstrated immunoreactivity to MMP-9. This investigation demonstrated increased MMP-9 proteinase activity and tPA protein levels in the walls of AAAs, as well as inflammatory leukocyte invasion of the adventitia and media compared to controls. These data suggest that leukocyte-derived MMP-9 is associated with aortic wall degeneration and aneurysm formation. Furthermore, activation of MMP-9 may be caused by increased tPA levels in the walls of AAAs.     

The role of estrogen in the formation of experimental abdominal aortic aneurysm

Objective

The current study sought to investigate the role of estrogen in the formation of experimental abdominal aortic aneurysm (AAA).

Methods

Elastase perfusion of infrarenal AAA animal model was performed in 20 female and 20 male Wistar rats that were randomly divided into an ovariectomized/sham-operated group and an estradiol (E2) experimental/saline control group, respectively. At day 14, E2 was detected, while the mRNA and protein expressions of matrix metalloproteinases 2 and 9 (MMP-2 and -9) in AAA tissue were detected by immunohistochemistry and polymerase chain reaction (PCR).

Results

The ovariectomized group showed lower estrogen levels and a higher aneurysm dilatation rate and significantly higher MMP-2 and -9 expression compared with the sham-operated group (P < .01), which was in accordance with MMP-2 and -9 mRNA expression. The E2 group showed higher estrogen levels and a lower aneurysm dilatation rate and significantly lower MMP-2 and -9 expression than did the saline control group (P < .01), which was in accordance with MMP-2 and -9 mRNA expression.

Conclusions

In the pathogenesis of AAA, estrogen may play an inhibitory role by decreasing expression of MMP-2 and MMP-9 synthesis.     

MMP-12 has a role in abdominal aortic aneurysms in mice

BACKGROUND: Matrix metalloproteinase (MMP)-12 levels are increased in the abdominal aortic aneurysm (AAA), implicating this protease in AAA pathogenesis. The purpose of this study was to assess the role of MMP-12 in aneurysm formation. METHODS: A murine aneurysm model was generated by periaortic application of 0.25 mol/L calcium chloride (CaCl 2 ) for 15 minutes. Aortic diameters were measured and compared before and 10 weeks after aneurysm induction. Aortic diameter changes for wild type (WT) and MMP-12 knockout (MMP-12 -/- ) mice were determined. MMP-12 production in mouse aorta was analyzed by casein zymography. MMP-2 and MMP-9 expressions were examined by gelatin zymography. Immunohistochemical study was used to measure macrophage infiltration into the aorta. RESULTS: There is an increase of 63 +/- 5% (mean +/- SEM) in aortic diameters of WT mice after CaCl 2 inductions, while MMP-12 -/- mice increased only 26 +/- 14%. Connective tissue staining of aortic sections from WT mice showed disruption and fragmentation of medial elastic fibers, while MMP-12 -/- mice showed only focal elastic lamellae breakdown. MMP-12 levels in WT mice were significantly increased after CaCl 2 treatment, whereas no MMP-12 was detected in MMP-12 -/- mice. There was no difference in the MMP-2 and MMP-9 productions between WT and MMP-12 -/- mice. Immunohistochemical analysis demonstrated that infiltrating macrophages in the aorta of MMP-12 -/- mice were significantly less than WT controls. CONCLUSIONS: MMP-12 deficiency attenuates aneurysm growth, possibly by decreasing macrophage recruitment.