Stromelysin Research Articles

ST2 and galectin-3 as novel biomarkers for the prediction of future cardiovascular disease risk in preeclampsia

The aim of this study was to investigate known cardiovascular disease (CVD) risk biomarkers galectin-3 (Gal-3) and human stromelysin-2 (ST2) levels in preeclampsia (PE) and normotensive pregnancies. A case-control study was conducted in a teaching and research hospital. We performed data analysis involving 45 pregnant women with PE and gestational week (GW) matched 35 normotensive pregnant women. The Gal-3 and ST2 levels were determined by using ELISA kit. Gal-3 values did not differ statistically between PE and control groups (535.1 ng/mL vs. 615.2 ng/mL) (p> .05). ST2 value in the PE group was statistically significantly lower than the control group (33.3 pg/mL vs. PE, 54.5 pg/mL, p ˂ .05). >34 GW patients (late-onset PE) had statistically significantly lower Gal-3 values than the ≤34 GW patients (early-onset PE) (507.1 ng/mL vs. 769.6 ng/mL, p ˂ .05). Late-onset PE patients had significantly lower ST2 values than early-onset patients (26.4 pg/mL vs. 57.9 pg/mL, p ˂ .05). We assume that low Gal-3 values in early-onset PE show a higher risk of cardiac fibrosis although both early and late-onset PE patients had an increased CVD risk later in life. We found the superiority of ST2 levels to Gal-3 levels in PE pregnancies for CVD risk assessment. Impact Statement What is already known about this subject? Preeclampsia (PE) in pregnancy is a known risk factor for future cardiovascular disease (CVD) and is also associated with increased mortality from ischaemic heart disease later in life. Studies that investigate patients with a higher risk for CVD in PE pregnancies are lacking. What do the results of this study add? We found different levels of two novel cardiac markers with PE and normotensive pregnancies, and also with early and late-onset PE pregnancies. What are the implications of these findings for clinical practice and/or further research? Different adaptive responses from patients during PE pregnancies via altered levels of cardiac markers could help clinicians to identify women with a higher risk of CVD.

Study of three novel biomarkers, MR-proADM, midkine, and stromelysin2, and peripheral atherosclerosis in a Chinese Han population: A case-control study

Midregional pro-adrenomedullin (MR-proADM), midkine, and stromelysin2 (ST2) are novel cardiac biomarkers associated with heart failure and atherosclerotic diseases like stable ischemic disease and acute coronary syndrome. The potential association between these three biomarkers and peripheral artery disease (PAD) remains unclear. The aim of this study was to assess the correlation between these three biomarkers and their association with PAD in the Chinese Han population. This study included 224 patients suspected of having coronary artery disease (CAD). All subjects underwent coronary angiography and carotid and subclavian ultrasound assessment for detection of coronary and peripheral atherosclerosis and were divided into two groups according to whether they had PAD or not. Pearson’s correlation coefficient r was calculated, and multivariable logistic regression analysis was conducted to represent the associations of these biomarkers and PAD. The study included 133 patients with PAD and 91 non-PAD controls and these two groups had similar values for age, ST2, hematocrit, hemoglobin, red blood cell counts, creatinine and CAD ratio, smoking, and type 2 diabetes (all p > 0.05). Compared with non-PAD controls, patients with PAD had lower levels of MR-proADM and midkine and higher levels of TC, LDL-C, and fasting blood sugar (FBS) (all p < 0.05). MR-proADM was positively and ST2 negatively correlated with midkine (all p < 0.05). Compared with females, male patients had higher values of MR-proADM ( p < 0.05) and similar levels of ST2 and midkine (all p > 0.05). Multivariable regression analysis identified FBS as a risk predictor (OR: 1.163, 95% CI: 1.108–1.401, p = 0.014) and MR-proADM as a protective factor (OR: 0.720, 95% CI: 0.529–0.920, p = 0.037) of PAD. Three novel biomarkers, MR-proADM, midkine, and ST2, are internally related, and MR-proADM is gender-specific and a protective factor of peripheral atherosclerosis in the Chinese Han population studied. Clinical Trial: ChiCTR-DDD-17013908

Fungsi-Fungsi Manajemen Dalam Pengelolaan Kurikulum

Madrasa need good curriculum management so that the objectives of implementing Islamic education can be effective and efficient. Curriculum Management is a curriculum management system to provide benefits to users who have been included in the prescribed curriculum. This study aims to uncover management functions including planning, organizing, actuating, and controling the curriculum at MI Miftahul Huda Bandung, MI At-Taqwa Bandung and MIT PERSIS 24 Bandung. The research method used is a qualitative method. The results of the study show that (1) Curriculum planning St MI Miftahul Huda was carried out through two stages carried out by the madrasa division. While the increase in the curriculum at MI At-Taqwa and MIT PERSIS 24 was only carried out by Madrasas at curriculum development meetings. (2) Organizing using the same curriculum design pattern with curriculum based on subjects (subject curriculum). (3) Actuating of three Madrasas The implementation of learning that began since (4) Controlling was carried out on Students and Educators through supervision 1 or 3 months by the division of education and supervision by Madrasah heads.

The Role of Stromelysin-3 (ST-3) in Progression of Oral Squamous Cell Carcinoma- A Narrative Review

The Role of Stromelysin-3 (ST-3) in Progression of Oral Squamous Cell Carcinoma- A Narrative Review

Paclitaxel-eluting stents versus everolimus-eluting coronary stents in a diabetic population: two-year follow-up of the TUXEDO-India trial.

The aim of this study was to report whether the superiority of the everolimus-eluting stent (EES) vs. the paclitaxel-eluting stent (PES) at one-year follow-up in the Taxus Element versus Xience Prime in a Diabetic Population (TUXEDO)-India trial was sustained at longer-term follow-up. One thousand eight hundred and thirty (1,830) patients with diabetes mellitus and coronary artery disease were randomised to EES vs. PES. Follow-up data up to two years were available in 1,701 (92.9%) patients. The primary endpoint was target vessel failure (TVF), defined as the composite of cardiac death, target vessel myocardial infarction (TV-MI), or ischaemia-driven target vessel revascularisation (TVR). Treatment with EES had a lower two-year rate of TVF (4.3% vs. 6.6%, p=0.03). Of the secondary endpoints, EES significantly reduced any MI (1.6% vs. 3.5%, p=0.01), TV-MI (0.7% vs. 3.1%, p=0.0001), ST (0.4% vs. 2.2%, p=0.001), cardiac death or target vessel MI (2.9% vs. 4.8%, p=0.04) and TLR (1.9% vs. 3.7%, p=0.02), compared with PES. Between one year and two years, no significant differences in the clinical outcomes were observed (pinteraction >0.05). In this adequately powered trial, the benefits of EES vs. PES in a diabetic population seen at one year were maintained at two years.

Serial serum soluble stromelysirn-2 testing to assess prognosis in elderly patients with acute heart failure

Objective To investigate the predicting value of serial serum human stromelysin-2(ST2)testing on prognosis in elderly patients with acute heart failure(AHF). Methods 75 AHF patients aged 60 to 90 were selected in our study who were in Beijing Hospital during 2013.1~2014.8, blood sampling of serum ST2 took place at admission and 72-96 h later.Moreover, 38 healthy people aged 70 to 80 were chosen as control group.Follow-up was performed 1 year after acute attack.We defined the end of observation as recurrence of heart failure or any cause of death.The data was analyzed by SPSS19.0. Results Among 55 AHF patients, sST2 level was higher in patients with endpoint events than those without it on the two moment(P=0.000). And we found that the change in sST2 was higher in patients with endpoint events than those without it(P=0.023); and the percentage change in sST2 was also significantly different(P=0.033). Receiver operator curve analysis of the change in sST2 from baseline to 72-96 h later was strongly reflective of prognosis with area under the curve(AUC) of 0.696(P=0.013). And the change in sST2 Combined with the sST2 level at admission to predict the prognosis of AHF, the result would be more exciting, the area under the receiver operating characteristic(ROC)curve is 0.861(P<0.001). The endpoint event rate of the patients whose level of sST2 at admission was below 1408 ng/L and the change level in sST2 below 101 ng/L was 21.4%(3/14), while the data in patients whose level of sST2 at admission is above 1 408 ng/L and the change level in sST2 above 100 ng/L was 85.7%(12/14). Conclusions in elderly patients of AHF, sST2 elevate markedly.The result shows that the level of sST2 may be used to evaluate AHF prognosis.And the change in sST2 are able to predict the prognosis of AHF.Compared with NT-proBNP, serial sST2 testing appears to be a promising candidate for monitoring these patients. Key words: Receptors, interleukin; Heart failure; Prognosis

Protein Expression of Stromelysin-2 in Head and Neck Squamous Cell Carcinomas.

Some matrix metalloproteinases (MMPs) are involved in invasion and metastasis of head and neck squamous cell carcinoma (HNSCC). However, there are few studies on association between stromelysin-2 (ST-2) and invasive behavior of HNSCC. The purpose of this study was to investigate Stromelysin-2 expression by immunohistochemistry. This study was conducted on 81 specimens, including 61 HNSCC and 20 non neoplastic epithelium. Sections with 5 micron thickness were prepared and stained with immunohistochemistry technique. Then expression of ST-2 was evaluated according to percentage of stained cells and intensity of staining. Data were analyzed by SPSS (V.21) using Kruskal-Wallis and Tukey tests (P<0.05). The 61 HNSCC specimens were grades I 36.1%, II 34.4% and III 29.5%. The level of ST-2 expressions were moderate (++) and intensive (+++) in 21.3% and 78.7% of tumors, respectively. The ST-2 expression level was only significant between the tumors with grade I and grade III (P=0.016). Tumors presented ST-2 expression with staining intensity of mild 6.6%, moderate 26.2% and strong 67.2%. Staining intensity of ST-2 in grade I tumors was significantly lower than grade II and grade III (P<0.05), and there was no significant difference between grades II and III (P=0.99). According to this study, the expression of ST-2 is associated with histopathological grade and tumor differentiation in HNSCCs.

Recombinant canine stromelysin 3 inhibits drug induced apoptosis in vitro

Matrix metalloproteinases (MMPs) are zinc metalloproteases having a pivotal role in extracellular matrix degradation, tumor growth, apoptosis, angiogenesis, invasion, and development of metastases. Stromelysin 3 (ST3) increased tumor take by suppressing cell apoptosis. Our present goal was to set up an in vitro model in which we could study this new function of ST3. For this purpose, we analysed effect of vinblastine, an anti-cancer drug, on ST3 treated MDCK (Madin-Darby canine kidney) cells. We found a marked decrease in the percentage of vinblastine induced MDCK cell death when the cells were pre-treated with recombinant ST3 as assessed by FACS analysis. Our data confirmed and extended the anti-apoptotic function of ST3 in-vitro.

Regulation of carthamus tinctorius on gene expression of stromelysin-1 and tissue inhibitor of metalloproteinase-1 in HSC-T6 cells

Objective To investigate the effects of carthamus tinctorius on gene expression of stromelysin-1 (MMP3) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in HSC-T6 cells.Methods HSC-T6 cells were cultured in the medium containing different concentrations of carthamus tinctorius (1.0,and 0.5 g/L) and collected after incubation for 48 h.Total RNA of HSC-T6 cells was isolated and gene expression levels of MMP3 and TIMP-1 were measured by using reverse transcription polymerase chain reaction (RT-PCR).Results MMP3 gene expression levels in 1.0 and 0.5 g/L carthamus tinctorius groups were 2.80 ±0.36 and 2.52 ±0.32 respectively,and that in control group was 2.13 ±0.30.TIMP-1 gene expression level in 1.0 and 0.5 g/L carthamus tinctorius groups were 1.66 ± 0.23 and 2.04 ± 0.30 respectively,and that in control group was 4.03 ± 0.56.Conclusion Carthamus tinctorius may enhance the expression of MMP3,but significantly inhibit TIMP-1 gene expression of HSC-T6 cells in a concentration-dependent manner. Key words: Hepatic stellate cell; Carthamus tinctorius; Stromelysin-1; Tissue inhibitor of metalloproteinase-1 ; Gene expression

IGFBP7, a novel immunohistochemical marker in differentiating dermatofibroma from dermatofibrosarcoma protuberans

Loss of insulin-like growth factor-binding protein 7 (IGFBP7) has been found to be a critical step in the development of melanoma and colon cancer. To our knowledge, immunostaining of IGFBP7 in various dermatofibrosarcoma protuberans (DFSP) and dermatofibroma (DF) has not been studied before. To assess the immunostaining of IGFBP7 in DFSPs and DFs and to ascertain whether IGFBP7 is superior to antibodies traditionally used in differentiating DFs from DFSPs. Immunohistochemical staining was performed on 28 cases of DFSP and 30 cases of DF, using antibodies to IGFBP7, CD34, factor XIIIa (FXIIIa), CD10 and stromelysin-3 (ST-3). Six of 28 (21.4%) DFSP samples were positive for IGFBP7, whereas 28 of 30 (93.3%) DF samples were positive. CD34 was positive in 26 of 28 (92.9%) cases of DFSP and 4 of 30 (13.3%) cases of DF. FXIIIa staining was positive in 4 of 28 (14.3%) cases of DFSP and 28 of 30 (93.3%) cases of DF. CD10 staining was positive in 12 of 28 (42.9%) cases of DFSP and ST-3 staining was positive in 7 of 28 (25.0%) cases of DFSP. The preferential IGFP7 staining of DFSPs in comparison with DFs was statistically significant (P < 0.01). We confirmed that IGFBP7 is a negative immunohistochemical marker for DFSPs and the combination with CD34, FXIIIa and ST-3 immunostaining could make the distinction more reliable.

Vernolide-A inhibits tumour specific angiogenesis by regulating proinflammatory cytokines, VEGF, MMPs and TIMP

Angiogenesis is the development of new blood vessels from the pre-existing vascular beds, and plays a pivotal role in tumour growth, invasion and metastasis. We studied the antiangiogenic activity of vernolide-A using in vivo as well as in vitro models. Vernolide-A significantly inhibited tumour directed capillary formation. The level of serum proinflammatory cytokines such as IL-1β, IL-6, TNF-α, and GM-CSF, and also level of serum VEGF, a proangiogenic factor were found to be elevated in angiogenesis induced animals which were significantly reduced by the treatment of vernolide-A in C57BL/6 mice. Administration of vernolide-A significantly enhanced the production of antiangiogenic factors such as IL-2 and TIMP. In vitro studies using rat aortic ring assay showed that vernolide-A at non-toxic concentrations significantly inhibited microvessel sprouting and also exhibited a significant inhibition in the proliferation, migration, and tube formation of endothelial cells, which are key events in the process of angiogenesis. Vernolide-A significantly inhibited the invasion of the collagen matrix by HUVECs in a dose dependent manner and also showed an inhibition in the activation of procollagenase to active collagenase of metalloproteinases. Taken together, these results demonstrate that vernolide-A inhibits tumour-specific angiogenesis by downregulating the production of pro-angiogenic factors like pro-inflammatory cytokines, VEGF, and MMPs and also upregulating the anti-angiogenic factors such as IL-2 and TIMP-1.

Collagen triple helix repeat containing-1 in the differential diagnosis of dermatofibrosarcoma protuberans and dermatofibroma

The distinction between dermatofibroma (DF) and dermatofibrosarcoma protuberans (DFSP) is a well-known challenge for dermatopathologists. Immunohistochemical stains have been used to augment routine histological examination to aid in differentiating DF from DFSP. Collagen triple helix repeat containing-1 (Cthrc1) was identified as a novel gene expressed in the adventitia and neointima on arterial injury. It is indicated to be a cell type-specific inhibitor of transforming growth factor-β, which in turn impacts collagen type I and III deposition, neointimal formation, and dedifferentiation of stem cells. Cthrc1 has also been shown to be highly active and potent in degrading extracellular matrix proteins and was found to be overexpressed in several malignant tumours, such as breast cancer and malignant melanoma. To our knowledge, however, expression of Cthrc1 in DFSP and DF has not been studied before. To assess the expression of Cthrc1 in DFSP and DF and to ascertain whether Cthrc1 is superior to antibodies traditionally used in differentiating DF from DFSP. Immunohistochemical staining was performed on 23 cases of DFSP and 35 cases of DF, using antibodies to Cthrc1, CD34, factor XIIIa, CD10 and stromelysin-3 (ST3). Twenty-two of 23 (96%) DFSP samples were positive for Cthrc1, whereas 32 of 35 (91%) DF samples were negative. CD34 was expressed in most DFSPs (22 of 23, 96%), whereas it was completely negative in most cases of DF (29 of 35, 83%). Expression of factor XIIIa was found in most cases of DF (33 of 35, 94%), whereas it was completely absent in 21 of 23 (91%) DFSP cases. Expression of CD10 was found in most cases of DF (30 of 35, 86%), whereas it was completely absent in 13 of 23 (57%) DFSP cases. ST3 was expressed strongly in most cases of DF (32 of 35, 91%), whereas it was completely absent in 18 of 23 (78%) DFSP cases. The preferential Cthrc1 staining of DFSP in comparison with DF was statistically significant (P < 0·01). We confirmed that Cthrc1 is a positive marker for DFSP and that Cthrc1 staining might be more reliable than markers traditionally used. Cthrc1 was not positive in absolutely [corrected] all cases of DFSP, and combination with CD34, factor XIIIa and ST3 immunostaining could make the distinction more reliable.

Reperfusion of old or new: left bundle branch block?

Reperfusion options for patients suffering ST-elevation myocardial infarction (STEMI) have developed significantly over recent years and now include both thrombolytic therapy and primary percutaneous coronary intervention (PPCI). This system of care means that patients presenting with STEMI can be transferred directly to a heart-attack centre to receive immediate PPCI. National guidelines state that pre-hospital thrombolysis (PHT) is a crucial part of STEMI reperfusion where PPCI cannot be delivered within 90 minutes of diagnosis. There is evidence describing rates of in-hospital thrombolysis in both MI with ST elevation and MI with LBBB. There is a knowledge gap however describing treatment of MI with LBBB based upon a pre-hospital 12-lead ECG. This paper describes the challenges around PHT in the context of LBBB and offers potential solutions that may provide assistance in making the decision to undertake PHT or not.

Markers of vascular differentiation, proliferation and tissue remodeling in juvenile nasopharyngeal angiofibromas

Juvenile nasopharingeal angiofibroma (JNA) is a histologically benign locally aggressive tumor characterized by irregular vessels embedded in a fibrous stroma. Excessive vascularity results in bleeding complications, and the inhibition of angiogenesis is a promising strategy for managing extensive JNA tumors. To better characterize the endothelial components of JNA, we aimed to evaluate markers of vascular differentiation and proliferation, such as friend leukemia integration-1 (FLI-1) and endoglin, lymphatic markers, including podoplanin and vascular endothelial growth factor receptor 3 (VEGFR3) and its cognate ligand VEGFC, GLUT-1, a diagnostic marker that discriminates between hemangiomas and vascular malformations, and two markers of tissue remodeling, stromelysin 3 (ST3) and secreted acid protein rich in cysteine (SPARC). Antigens were assessed immunohistochemically in vessels and stromal cells of JNA archival cases (n=22). JNA endothelial cells were positive for endoglin, VEGFC and FLI-1, whereas podoplanin and VEGFR3 were negative in all cases. Both endothelial cells and fibroblasts stained for ST3 and SPARC. GLUT-1 was investigated in JNA cases, in infantile hemangiomas (n=123) and in vascular malformations (n=135) as controls. JNAs and vascular malformations were GLUT-1-negative, while hemangiomas showed positive staining. The presence of markers of endothelial differentiation and proliferation highlighted the hyper-proliferative state of JNA vessels. The absence of podoplanin and VEGFR3 underscores their blood endothelial cell characteristic. The absence of GLUT-1 discriminates JNAs from hemangiomas. ST3 and SPARC up-regulation in endothelial cells and fibroblasts may contribute to a compensatory signaling for controlling angiogenesis. Some of these markers may eventually serve as therapeutic targets. Our results may aid in the understanding of JNA pathophysiology.

Expression of matrix metalloproteinases in full-term human umbilical cord and Human Umbilical Vein Endothelial Cells.

background Matrix metalloproteinases (MMPs) are extracellular zinc-dependent endopeptidases involved in breakdown and remodelling of extracellular matrix in physiological and pathological processes. MMPs have also a role on cell proliferation, migration, differentiation, angiogenesis and apoptosis. Umbilical cord is a special organ subjected to many changes during pre-natal life and whose cells can maintain a certain degree of plasticity also in post-natal period; for example recently they have been used as a source of stem cells. For these reasons we believe it is interesting to investigate the expression of some remodelling enzymes in this tissue. Human Umbilical Vein Endothelial cells (HUVEC) have shown to be endowed with an high degree of plasticity; they have the potentiality to differentiate into different cell types and can be considered one of the territories of umbilical cord more dynamic and involved in remodelling/renewal phenomena, for this reason we decided to extend our research investigating the expression of MMPs also in these cells. Aim In this study we investigated by immunohistochemistry and RT-PCR the expression of the gelatinases MMP-2 and MMP-9, the collagenases MMP-8 and MMP-13 and the stromelysin MMP-3 and MMP-10 in the whole human umbilical cord and in HUVEC. Results MMP-2 protein is expressed in the amniotic epithelium of human umbilical cord and in few sub-epithelial fibroblasts, while MMP-3 and MMP-10 only in the umbilical epithelium. MMP-8, MMP-9 and MMP-13 immunoreactivity is localised in the epithelium and in Wharton’s jelly mesenchymal cells. Immunohistochemistry also revealed protein expression for MMP-2, 3, 8, 9 and 10 in cultured Human Umbilical cord Vein Endothelial Cells. In agreement with immunohistochemical data, RT-PCR analysis performed on samples of whole umbilical cord confirmed the transcriptional expression for the genes encoding all the six matrix metalloproteinases investigated, while in HUVEC cells only the expression of MMP-2, 3, 9, 10 and 13 mRNAs was detected.

Acronym Madness – Part 2

Medical acronym use has become almost a necessary part of discussions of advances in cardiovascular medicine. All acronyms are simply abbreviations – usually in upper case (as in NATO) but sometimes not (as in radar). Medical acronyms tend to be formed from single words found in the name of a programme (CHEP for Canadian Hypertension Education Program, MAUDE for a cardiovascular database of the FDA, SEARCH for a collaborative group [1], CHAMP for the Cardiovascular Health Awareness and Management Program) or formed from letters in words used in the title of a clinical study or trial (as in the DREAM study) (2). In the broad area of cardiovascular medicine research studies, one can find hundreds of acronyms, some very easy to pronounce (CHEP, HOPE, etc). For the most part, no strict rules apply to their derivation because the acronyms from some studies may have little meaning taken alone and may not constitute a word (as in the IPPSH study) (3). Acronyms may contain a word and number (TIMI-II study) (4), or designate an ST segment MI (STEMI). There are new cardiovascular study acronyms created almost every week and one can have fun with them. In 2004, a two-act play called “Acronym Madness”, containing 221 English acronyms from a broad range of cardiovascular studies, was published in The Canadian Journal of Cardiology (CJC) (5). Since then, many new cardiovascular study acronyms have appeared. Two hundred thirty-one new acronyms, previously unused as well as some from the original play, were chosen for use in the sequel. The basis for the creation of such plays is humour. Laughter may still be the best medicine. A synopsis of the original play, using the previous acronyms, will be helpful. Dr CARLOS D HANE of MIAMI, FLORIDA, with a PhD from SIAM University and an MD from the University of EPHESUS, applied for a position as house physician at the ACUTE COMA Hospital in London, England, in 2004. His interview with a Prof ADAM PARK had gone poorly. PARK judged his curriculum vitae (CV) to be seriously flawed. HANE admitted to being a keen ACRONYM collector but his research claims were suspect and his rapport was less than ideal. He failed the interview and did not get the position. Undeterred, CARLOS D HANE has now applied for a hospital position in Nova Scotia. A transcript of his latest interview follows.

Age-related changes in activity of proteoglycanase in cervical discs

Objective Experimental study on age-related changes in activities of proteoglycanases obtained from various cervical intervertebral discs. Methods 40 spcimens were analysed, among these lumbar intervertebral discs, 10 were fetal cevical intervertebral discs, 10 were 17-25 years-old cervical in-tervertebral discs, 10 were 40-55 years-old cervical intervertebral discs, 10 were 60-75 years-old cervical intervertebral discs. Proteoglycansaes were extracted with 0.05 mmol/L Tris/HCl buffer which contains 10.0 mmol/L CaCl_2. The proteoglycan of bovine scapula cartilage extracted with 4.0moL/L Guanidine HCI was used as substrate. The proteoglyean breakdown of the reaction indicated the activity of the proteogly-canases from various luumbar intervertebral discs. Results Activities of proteoglycanases from fetal discs,17-25 years-old discs,40-55 years-old discs and 60-75 years-old discs were 1.911±0.21,0.881±0.155,1. 720±0.19,1. 777±0.142. Conclusion Levels of Proteoglycansae were age-related and may play a important role in the pathological process of degeneration of cervical intervertebral discs. Key words: Proteoglycanase; Matrix metalloroteinase; Activity; Cervical interverteral disc

Differential Regulation of Cell Type-specific Apoptosis by Stromelysin-3: A POTENTIAL MECHANISM VIA THE CLEAVAGE OF THE LAMININ RECEPTOR DURING TAIL RESORPTION IN XENOPUS LAEVIS

Matrix metalloproteinases (MMPs) have been extensively studied because of their functional attributes in development and diseases. However, relatively few in vivo functional studies have been reported on the roles of MMPs in postembryonic organ development. Amphibian metamorphosis is a unique model for studying MMP function during vertebrate development because of its dependence on thyroid hormone (T3) and the ability to easily manipulate this process with exogenous T3. The MMP stromelysin-3 (ST3) is induced by T3, and its expression correlates with cell death during metamorphosis. We have previously shown that ST3 is both necessary and sufficient for larval epithelial cell death in the remodeling intestine. To investigate the roles of ST3 in other organs and especially on different cell types, we have analyzed the effect of transgenic overexpression of ST3 in the tail of premetamorphic tadpoles. We report for the first time that ST3 expression, in the absence of T3, caused significant muscle cell death in the tail of premetamorphic transgenic tadpoles. On the other hand, only relatively low levels of epidermal cell death were induced by precocious ST3 expression in the tail, contrasting what takes place during natural and T3-induced metamorphosis when ST3 expression is high. This cell type-specific apoptotic response to ST3 in the tail suggests distinct mechanisms regulating cell death in different tissues. Furthermore, our analyses of laminin receptor, an in vivo substrate of ST3 in the intestine, suggest that laminin receptor cleavage may be an underlying mechanism for the cell type-specific effects of ST3.

Mutational analysis of the cleavage of the cancer-associated laminin receptor by stromelysin-3 reveals the contribution of flanking sequences to site recognition and cleavage efficiency

The matrix metalloproteinase stromelysin-3 (ST3) has long been implicated to play an important role in cell fate determination during normal and pathological processes. Using the thyroid hormone-dependent Xenopus laevis metamorphosis as a model, we have previously shown that ST3 is required for apoptosis during intestinal remodeling and that laminin receptor (LR) is an in vivo substrate of ST3 during this process. ST3 cleaves LR at two distinct sites that are conserved in mammalian LR. Human ST3 and LR are both associated with tumor development and cancer progression and human LR can also be cleaved by ST3, implicating a role of LR cleavage by ST3 in human cancers. Here, we carried out a series of mutational analyses on the two cleavage sites in LR. Our findings revealed that in addition to primary sequence at the cleavage site (positions P3-P3', with the cleavage occurring between P1-P1'), flanking sequences/conformation also influenced the cleavage of LR by ST3. Furthermore, alanine substitution studies led to a surprising finding that surrounding sequence and/or conformation dictated the site of cleavage in LR by ST3. These results thus have important implications in our understanding of substrate recognition and cleavage by ST3 and argue for the importance of studying ST3 cleavage in the context of full-length substrates. Furthermore, the LR cleavage mutants generated here will also be valuable tools for future studies on the role of LR cleavage by ST3 in vertebrate development and cancer progression.

Effect of Length and Diameter of Drug-Eluting Stents Versus Bare-Metal Stents on Late Outcomes

Background— The risk of restenosis and other adverse cardiac events with bare-metal stents (BMS) is increased with smaller stent diameters and longer stent lengths. Drug-eluting stents (DES) may reduce this effect in select patients; however, whether this benefit occurs in high-risk lesions and patients in routine practice is not clear. Methods and Results— Clinical outcomes (target-vessel revascularization [TVR], stent thrombosis, nonfatal myocardial infarction [MI], and cardiac death) at 2 years stratified by stented length and diameter were compared in 949 consecutive patients who received BMS and 1236 consecutive and comparable patients who received DES for single lesions. The longest tertile of BMS (&gt;23 mm) was associated with increased hazard of TVR, ST, and nonfatal MI or death compared with shorter tertiles of BMS, which was abolished by DES. DES compared with BMS was independently associated with a lower hazard of TVR (HR, 0.34 [0.20 to 0.58]) and nonfatal MI or death (HR, 0.60 [0.39 to 0.92]) in the longest length tertile (&gt;23 mm). No clear association of stented tertile diameter and clinical outcomes for either stent type was observed. However, DES compared with BMS was independently associated with a lower hazard of TVR for all diameter tertiles, and a lower hazard of nonfatal MI or death (0.66 [0.44 to 0.99]) in the largest diameter tertile (&gt;3.4 mm). Conclusions— Independent of adverse patient and lesion characteristics, DES demonstrated significantly lower hazard of TVR and nonfatal MI or death at 2 years compared with BMS within the longest stented lengths (&gt;23 mm) and largest diameters (&gt;3.4 mm).