scholarly journals Expression of osteopontin, matrix metalloproteinase-2 and -9 proteins in vascular instability in brain arteriovenous malformation

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7058 ◽  
Author(s):  
Lalita Anbarasen ◽  
Jasmine Lim ◽  
Retnagowri Rajandram ◽  
Kein Seong Mun ◽  
Sheau Fung Sia

Background Matrix metalloproteinase (MMP)-2 and -9 are Osteopontin (OPN) dependent molecules implicated in the destabilization of blood vessels. OPN and MMPs have been studied in brain arteriovenous malformation (BAVM) patients’ tissues and blood samples before intervention. In this study, we compared the serum level of these markers before and after treatment, as well as assessed their protein expressions in BAVM tissues to evaluate their roles in this disease. Methodology Serum samples from six BAVM patients and three control subjects were analyzed using enzyme-linked immunoabsorbent assay (ELISA) for OPN. A total of 10 BAVM patients and five control subjects were analyzed using Multiplex ELISA for MMPs. A total of 16 BAVM tissue samples and two normal brain tissue samples were analyzed using immunohistochemistry. Result MMP-2 and -9 were significantly higher in the serum of BAVM patients before and after treatment than in control patients. There were no significant differences of OPN and MMP-9 serum level in BAVM patients before and after treatment. MMP-2 showed a significant elevation after the treatment. Expression of OPN, MMP-2 and -9 proteins were seen in endothelial cells, perivascular cells and brain parenchyma of BAVM tissues. Conclusion Findings revealed that the level of MMP-2 and -9 in the serum correlated well with the expression in BAVM tissues in several cases. Knockdown studies will be required to determine the relationships and mechanisms of action of these markers in the near future. In addition, studies will be required to investigate the expression of these markers’ potential applications as primary medical therapy targets for BAVM patients.


2014 ◽  
Vol 121 (6) ◽  
pp. 1478-1482 ◽  
Author(s):  
İlker Coven ◽  
Ozge Ozer ◽  
Ozlem Ozen ◽  
Feride İffet Şahin ◽  
Nur Altinors

Object Meningiomas are benign extraaxial tumors with a slow progression. Some of them, in spite of being benign in nature, may show an aggressive progression pattern. To investigate the behavioral characteristics of meningiomas, researchers have studied matrix metalloproteinases (MMPs), their tissue inhibitors (TIMPs), interstitial collagens, proteins, vascular endothelial growth factors (VEGF), and tumor necrosis factors. Methods In this study, the authors investigated MMP2 and TIMP2 gene polymorphisms in formalin-fixed paraffin-embedded tissue samples obtained from meningioma patients who had previously undergone surgery at the authors' institution. In addition, brain invasion, Ki-67 index, and MMP-2 and TIMP-2 expressions were investigated using immunohistochemical methods. MMP2 (735C>T, 1575G>A, 1306C>T) and TIMP2 (418G>C, 303C>T) gene polymorphisms were investigated from paraffin-embedded tissue sections using the polymerase chain reaction–restriction fragment length polymorphism method. Results There were statistically significant differences between genotype (p = 0.001) and allele frequencies (p = 0.001 and OR 7.4 [95% CI 1.5–36.2]) in patient and control groups for MMP2 1306C>T polymorphism. The authors did not find a statistically significant difference for other polymorphisms. GA genotype was found to be more frequent when brain invasion was suspected for MMP2 1575G>A polymorphism (p = 0.006). There was not a statistically significant difference for other MMP2 or TIMP2 gene polymorphisms. Conclusions The authors' results support the importance of MMPs and their tissue inhibitors in meningioma pathogenesis. In future studies, these gene polymorphisms, especially MMP2 1306C>T and 1575G>A, should be investigated for meningioma or brain invasion susceptibility in larger study groups.



1980 ◽  
Vol 59 (5) ◽  
pp. 385-387 ◽  
Author(s):  
G. Birgegård

1. Serum samples were collected from ten patients hospitalized for acute infections and from a control group of seven normal subjects. Tissue ferritin was obtained by purification of ferritin from normal human liver and from the ferritin standard of a commercially available assay kit. 2. The serum and tissue samples were incubated with concanavalin A-Sepharose, which has the ability to bind normal serum ferritin. 3. Concanavalin A, a plant lectin which binds to glucose, can be coupled to Sepharose particles and by incubation and centrifugation ferritin in normal serum can be absorbed to about 70%. The serum and tissue samples were incubated with concanavalin A-Sepharose and the ferritin content was measured before and after. 4. It was found that ferritin in the serum of patients with acute infections was absorbed to the same extent as in normal serum (about 80%), irrespective of the initial value. Only about 20% of the tissue ferritin was absorbed. 5. It is concluded that the ferritin in serum during infection is of the same glucosylated type as the ferritin normally present in serum, whereas intracellular ferritin is not glycosylated. This indicates that the elevation of serum ferritin during infection is caused by a release along the normal pathways, i.e. an augmented synthesis, not by leakage from damaged cells.



Biologia ◽  
2007 ◽  
Vol 62 (3) ◽  
Author(s):  
Albena Alexandrova ◽  
Elena Bandžuchová ◽  
Anton Kebis ◽  
Marián Kukan ◽  
Daniel Kuba

AbstractCopper is known to induce oxidative stress in a number of models. It was shown that many pathophysiological events were associated with oxidative stress. Further, oxidative stress can increase gene expression of cytokines and of metalloproteinases. We previously found that copper toxic effects in isolated perfused rat livers were associated with significant oxidative stress (as assessed by lipid peroxidation, protein oxidation and oxidative DNA damage, particularly at concentration of 0.03 mM of Cu2+ in the perfusate). Here we investigated gene expression of tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10); matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) in frozen liver tissue samples by the real-time PCR assay. Compared to controls, copper at concentration of 0.01 mM did not affect gene expression of TNF-α, IL-10, MMP-2 and MMP-9, whereas copper at concentration of 0.03 mM significantly decreased gene expression of all the four TNF-α, IL-10, MMP-2 and MMP-9 by 69%, 81%, 43%, and 62%, respectively. These results suggest that copper-induced oxidative stress in the isolated rat liver can lead to the suppression of gene expression. Because TNF-α and metalloproteinases are involved also in liver regeneration, the suppression of these genes by copper may be one of the mechanisms by which acute intoxication of animals and humans with copper may impair regenerative capability of the liver.



2015 ◽  
Vol 16 (15) ◽  
pp. 6749-6751 ◽  
Author(s):  
Alireza Lotfi ◽  
Ghodrat Mohammadi ◽  
Lale Saniee ◽  
Mehrnoosh Mousaviagdas ◽  
Hadi Chavoshi ◽  
...  


2006 ◽  
Vol 37 (10) ◽  
pp. 1316-1323 ◽  
Author(s):  
Paula Kuvaja ◽  
Anne Talvensaari-Mattila ◽  
Paavo Pääkkö ◽  
Taina Turpeenniemi-Hujanen


2020 ◽  
Author(s):  
Erman Kandilli ◽  
Şenay Görücü Yılmaz ◽  
Murat Yardımcı ◽  
Necla Benlier ◽  
Muradiye Nacak

Abstract BackgroundCardiovascular diseases (CVD) are among the causes of morbidity and mortality in the world. Significant advances have been made in the diagnosis, treatment and prognosis of CVD. New biomarkers and therapeutic targets are needed to reduce the incidence of this disease. Recently, there is growing evidence that circulating microRNAs can be used as diagnostic biomarkers in this disease. Methods We compared five microRNA (hsa-miR-21-5p, hsa-mi181a-5p, hsa-miR-199a-5p, hsa-miR-199b-5p and hsa-miR-320a) expression levels associated with ischemia/reperfusion before and after bypass graft surgery in serum samples of patients (N=46) with coronary artery disease and healthy control subjects (N=48). Expression measurements were made for each miRNA preoperatively and postoperatively at 1. and 24. hours, and then compared with the control subjects. Troponin I, creatine phosphate kinase and creatine kinase myocardial band cardiac markers were measured before and 1 and 24 hours postoperatively and compared to miRNA expressions and controls. Quantitative real-time PCR was used for expression analysis. The data were analyzed by Mann-Whitney test, chi-squared test, Logistic Regression analysis, and Kruskal-Wallis test with the statistical package SPSS. Results The five miRNAs were down-regulated compared to controls. The expression level for miR-199a at 24 h postoperatively was significantly lower than at 1 h (p=0.001). Receiver operating characteristic analysis showed that the area under the curve of miR-199a-5p was 0.810 (sensitivity 87% and specificity 68.5%) in preoperative patients. Conclusions: miR-199a and miR-199b in serum are a novel non-invasive biomarker candidate for coronary artery disease.



2020 ◽  
Vol 8 (B) ◽  
pp. 973-977
Author(s):  
Bagus Ngurah Mahakrishna ◽  
Eka Gunawijaya ◽  
I Wayan Dharma Artana ◽  
Ni Putu Veny Kartika Yantie ◽  
Made Kardana ◽  
...  

BACKGROUND: Left ventricular end-diastolic volume (LVEDV) on echocardiography is one of the tests performed on heart failure. This refers to the volume of the left ventricle at the end of the diastolic phase, which would be increased when there is a disturbance in preload, afterload, and contractility factors. Matrix metalloproteinase-2 (MMP2) is a marker of congestive heart failure that can be examined through laboratory examinations. AIM: The objective of the study was to provide evidence of the association between MMP and inflammatory process as well as its correlation with LVEDV in children with heart failure. METHODS: This was a cross-sectional study conducted on children aged 3 months–12 years old with heart failure, who visited Sanglah Hospital, Denpasar, Indonesia from May 2017 to March 2018. Echocardiographic examination (LVEDV) and blood samples were taken to measure the serum level of MMP2 on day 1 after the subjects were diagnosed with heart failure. RESULTS: A total of 32 subjects with heart failure were analyzed in this study. Acyanotic congenital heart defect (CHD) was the most common cause of heart failure, as observed in 23 subjects (71.9%). Characteristics data revealed that 24 subjects (75%) were underweight, 23 (71.9%) had cardiomegaly, and 22 (68.8%) had mild heart failure. Data analysis showed a moderate positive correlation between MMP2 levels with LVEDV after controlling for the influence of age (p = 0.02; r = 0.425). CONCLUSION: There was a moderate positive correlation between MMP2 level and LVEDV after controlling for the age factor.



2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e14687-e14687
Author(s):  
Lucia Lombardi

e14687 Background: Multiple metastasis is the predominant cause of colorectal cancer (CC) and pancreatic cancer (PC) related mortality. Chemokines receptors have been implicated in cancer metastatic process by directing the migration of tumour cells to sites of metastasis. However, their clinical relevance in gastrointestinal cancer has not been defined. The aim of our study was to evaluate the possible role of CXCR4 as prognostic factor in CC and PC. Methods: Quantitative determination of CXCR4 in serum samples were collected before and after surgery from 36 CC and 23 PC patients later treated with adjuvant (Ad) therapy or for metastatic (Meta) disease (19 Ad-and 17 Meta-CC; 15Ad-PC and 8 Meta-PC) and from 31 healthy controls (HC) enrolled as controls group, was performed by means of ELISA. Relative expression levels of CXCR4 in matched-pairs of tumour and adjacent normal tissue samples collected from the same 36 CC and 15 Ad-PC patients, were determined by means of qRT-PCR using the QuantiFast SYBR Green PCR kit. Results: Compared to HC, pre-operative CXCR4 serum levels were increased in both CC and PC patients. Post-operative serum levels were higher than those observed pre-operatively in 42% and 47% of patients with Ad- and Meta-CC, respectively. Conversely, in 53% and 50% of patients with Ad- and Meta-PC, CXCR4 serum levels decreased after surgical treatment. Furthermore, higher levels of CXCR4 were associated with advanced stages and in PC with lymph nodes involvement. In addition, CXCR4 was over-expressed in tumor compared to normal tissue in 42% and 41% of patients with Ad- and Meta-CC, and in 73% of patients with Ad-PC. In relation to clinical phenotype, all these patients had stage T3N1 disease in both disease. Conclusions: Our data showed that CXCR4 levels may be associated with tumor stage and disease progression in CC and PC patients. Further studies with larger samples size, might confirm the role for CXCR4 as prognostic factor and/or marker of patients’ response to therapy.



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