Navegando por Palavras-chave "Matrix metalloproteinases"
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- ItemSomente MetadadadosAbnormalities in Metalloproteinase Pathways and IGF-I Axis: A Link Between Birth Weight, Hypertension, and Vascular Damage in Childhood(Nature Publishing Group, 2010-01-01) Sesso, Ricardo de Castro Cintra [UNIFESP]; Franco, Maria do Carmo Pinho [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)BACKGROUNDAlthough numerous studies suggest an inverse relationship between birth weight and cardiovascular disease, the mechanistic basis of this phenomenon is not fully understood. Here, we postulate that alterations in plasma concentration of matrix metalloproteinases (MMPs) and growth factors might show different associations between birth weight, blood pressure levels, and vascular function.METHODSConcentrations of MMP-2 and its tissue inhibitor 2 (TIMP-2), MMP-9, and insulin-like growth factor-I (IGF-I) and its binding protein IGFBP-3 were measured in 64 children (34 boys, 30 girls).RESULTSSmall-for-gestational-age children exhibited elevated amounts of MMP-2, MMP-9, MMP-2/TIMP-2 ratio, MMP-9/TIMP-2 ratio, as well as lower concentration of IGF-I (P < 0.01), a known regulator of elastin synthesis. Similar findings were observed after adjustment for current age, gender, and race. the changes in the circulating levels of MMP-2, MMP-9, and IGF-I correlated significantly with birth weight, systolic blood pressure, and vascular function. Stepwise regression analysis demonstrated that MMP-2 was found to be an independent predictor of systolic blood pressure (R(2) = 0.08), whereas MMP-9 and birth weight were independent predictors of vascular dysfunction (R(2) = 0.38).CONCLUSIONSIt is possible that the association of fetal programming with elevated risk for vascular and metabolic disease in later life is, at least in part, mediated by perturbations in the MMP pathways.
- ItemSomente MetadadadosAnti-inflammatory properties of a heparin-like glycosaminoglycan with reduced anti-coagulant activity isolated from a marine shrimp(Elsevier B.V., 2008-11-01) Brito, Adriana S.; Arimateia, Dayse S.; Souza, Lucilla R.; Lima, Marcelo A.; Santos, Vanessa O.; Medeiros, Valquiria P. [UNIFESP]; Ferreira, Paula A.; Silva, Rodrigo A.; Ferreira, Carmen V.; Justo, Giselle Z. [UNIFESP]; Leite, Edda L.; Andrade, Giulianna P. V.; Oliveira, Fernanda W.; Nader, Helena B. [UNIFESP]; Chavante, Suely F.; Univ Fed Rio Grande do Norte; Universidade Federal de São Paulo (UNIFESP); Universidade Estadual de Campinas (UNICAMP)The anti-inflammatory properties of a heparin-like compound from the shrimp Litopenaeus vannamei are related. Besides reducing significantly (p < 0.001) the influx of inflammatory cells to injury site in a model of acute inflammation, shrimp heparin-like compound was able to reduce the matrix metalloproteinase (MMPs) activity in the peritoneal lavage of inflamed animals. Moreover, this compound also reduced almost 90% the activity of MMP-9 secreted by human activated leukocytes. Negligible anti-coagulant activities in aPPT assay and a poor bleeding potential make this compound a better alternative than mammalian heparin as a possible anti-inflammatory drug. (C) 2008 Elsevier B.V. All rights reserved.
- ItemAcesso aberto (Open Access)Contrasting effects of aliskiren versus losartan on hypertensive vascular remodeling(Elsevier B.V., 2013-08-20) Martins-Oliveira, Alisson; Castro, Michele Mazaron de; Oliveira, Diogo Marçal Machado de; Rizzi, Elen; Ceron, Carla Speroni; Guimaraes, Danielle; Reis, Rosana Inacio dos; Costa-Neto, Claudio Miguel; Casarini, Dulce Elena [UNIFESP]; Ribeiro, Amanda Aparecida [UNIFESP]; Gerlach, Raquel Fernanda; Tanus-Santos, Jose Eduardo; Universidade de São Paulo (USP); Universidade Federal de São Paulo (UNIFESP)Background: Hyperactivation of the renin-angiotensin system contributes to hypertension-induced upregulation of vascular matrix metalloproteinases (MMPs) and remodeling, especially in the two kidney, one clip (2K1C) hypertension model. We hypothesized that the AT(1)R antagonist losartan or the renin inhibitor aliskiren, given at doses allowing similar antihypertensive effects, could prevent in vivo vascular MMPs upregulation and remodeling, and collagen/elastin deposition found in 2K1C hypertension by preventing the activation of extracellular signal-regulated kinase 1/2 (ERK 1/2) and transforming growth factor-beta(1) (TGF-beta(1)). We also hypothesized that aliskiren could enhance the effects of losartan.Methods: 2K1C rats were treated with aliskiren (50 mg.kg(-1).day(-1)), or losartan (10 mg.kg(-1).day(-1)), or both by gavage during 4 weeks.Results: Aliskiren, losartan, or both drugs exerted similar antihypertensive effects when compared with 2K1C rats treated with water. Aliskiren reduced plasma renin activity in both sham and 2K-1C rats. Losartan alone or combined with aliskiren, but not aliskiren alone, abolished 2K1C-induced aortic hypertrophy and hyperplasia, and prevented the increases in aortic collagen/elastin content, MMP-2 levels, gelatinolytic activity, and expression of phospho-ERK 1/2 and TGF-beta(1). No significant differences were found in the aortic expression of the (pro) renin receptor.Conclusions: These findings show that although losartan and aliskiren exerted similar antihypertensive effects, only losartan prevented the activation of vascular profibrotic mechanisms and MMP upregulation associated with vascular remodeling in 2K1C hypertension. Our findings also suggest that aliskiren does not enhance the protective effects exerted by losartan. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
- ItemAcesso aberto (Open Access)Effect of photodynamic therapy on the extracellular matrix and associated components(Associação Brasileira de Divulgação Científica, 2007-08-01) Pazos, Marcelo de Castro [UNIFESP]; Nader, Helena Bonciani [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)In many countries, photodynamic therapy (PDT) has been recognized as a standard treatment for malignant conditions (for example, esophageal and lung cancers) and non-malignant ones such as age-related macular degeneration and actinic keratoses. The administration of a non-toxic photosensitizer, its selective retention in highly proliferating cells and the later activation of this molecule by light to form reactive oxygen species that cause cell death is the principle of PDT. Three important mechanisms are responsible for the PDT effectiveness: a) direct tumor cell kill; b) damage of the tumor vasculature; c) post-treatment immunological response associated with the leukocyte stimulation and release of many inflammatory mediators like cytokines, growth factors, components of the complement system, acute phase proteins, and other immunoregulators. Due to the potential applications of this therapy, many studies have been reported regarding the effect of the treatment on cell survival/death, cell proliferation, matrix assembly, proteases and inhibitors, among others. Studies have demonstrated that PDT alters the extracellular matrix profoundly. For example, PDT induces collagen matrix changes, including cross-linking. The extracellular matrix is vital for tissue organization in multicellular organisms. In cooperation with growth factors and cytokines, it provides cells with key signals in a variety of physiological and pathological processes, for example, adhesion/migration and cell proliferation/differentiation/death. Thus, the focus of the present paper is related to the effects of PDT observed on the extracellular matrix and on the molecules associated with it, such as, adhesion molecules, matrix metalloproteinases, growth factors, and immunological mediators.
- ItemAcesso aberto (Open Access)F-18-Fluorodeoxyglucose positron emission tomography and serum cytokines and matrix metalloproteinases in the assessment of disease activity in Takayasu's arteritis(Elsevier Science Inc, 2016) Arraes, Anne E. D. [UNIFESP]; de Souza, Alexandre W. S. [UNIFESP]; Mariz, Henrique A. [UNIFESP]; Silva, Neusa P. [UNIFESP]; Torres, Ivone C. G.; Pinto, Paula N. V.; Lima, Eduardo N. P.; Sato, Emilia I. [UNIFESP]Objective: To evaluate F-18-fluorodeoxyglucose (FDG) uptake on positron emission tomography-computed tomography (PET-CT)-and serum levels of different cytokines and matrix metalloproteinases (MMPs) in patients with Takayasu's arteritis (TA) and associations with disease activity. Methods: Serum levels of tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-2, IL-6, IL-8, IL-12, IL-18, MMP-3 and MMP-9 were measured in 36 TA patients and 36 controls. Maximum standard uptake value (SUVmax) of 18F-FDG in arterial walls was determined by PET-CT scans. TA patients were classified as active disease, inactive disease and possible active disease. Results: Serum IL-6 and MMP-3 levels were higher in TA patients than in controls (p < 0.001). Serum IL-6 was higher in patients with active disease and in patients with possible active disease than in inactive disease (p < 0.0001). Patients with active disease had higher serum TNF alpha levels than patients with inactive disease (p = 0.049) while patients with possible active disease presented higher IL-18 levels than patients with inactive disease (p = 0.046). Patients with active disease had higher SUVmax values than those with inactive disease (p = 0.042). By ROC curve SUVmax was predictive of active disease in TA and values = 1.3 were associated with disease activity (p = 0.039). Serum TNF-alpha levels were higher in patients with SUVmax = 1.3 than < 1.3 (p = 0.045) and controls (p = 0.012). Serum IL-6 levels were higher in patients with SUVmax = 1.3 than in controls (p < 0.001). No differences regarding other biomarkers were found between TA patients and controls. Conclusions: Higher serum IL-6 and TNF alpha levels as well as higher arterial 18F-FDG uptake are associated with active TA. (C) 2015 Elsevier Editora Ltda.
- ItemSomente MetadadadosFibroblast and prostate tumor cell cross-talk: Fibroblast differentiation, TGF-beta, and extracellular matrix down-regulation(Elsevier B.V., 2010-11-15) Coulson-Thomas, Vivien Jane [UNIFESP]; Gesteira, Tarsis F.; Coulson-Thomas, Yvette May [UNIFESP]; Vicente, Carolina M.; Tersariol, Ivarne L. S.; Nader, Helena B.; Toma, Leny; Universidade Federal de São Paulo (UNIFESP)Growth and survival of tumors at a site of metastasis involve interactions with stromal cells in the surrounding environment. Stromal cells aid tumor cell growth by producing cytokines as well as by modifying the environment surrounding the tumor through modulation of the extracellular matrix (ECM). Small leucine-rich proteoglycans (SLRPs) are biologically active components of the ECM which can be altered in the stroma surrounding tumors. the influence tumor cells have on stromal cells has been well elucidated. However, little is understood about the effect metastatic cancer cells have on the cell biology and behavior of the local stromal cells. Our data reveal a significant downregulation in the expression of ECM components such as collagens I, II, III, and IV, and the SLRPs, decorin, biglycan, lumican, and fibromodulin in stromal cells when grown in the presence of two metastatic prostate cancer cell lines PO and DU145. Interestingly, TGF-beta down-regulation was observed in stromal cells, as well as actin depolymerization and increased vimentin and alpha 5 beta 1 integrin expression. MT1-MMP expression was upregulated and localized in stromal cell protrusions which extended into the ECM. Moreover, enhanced stromal cell migration was observed after crosstalk with metastatic prostate tumor cells. Xenografting metastatic prostate cancer cells together with activated stromal cells led to increased tumorigenicity of the prostate cancer cells. Our findings suggest that metastatic prostate cancer cells create a metastatic niche by altering the phenotype of local stromal cells, leading to changes in the ECM. (C) 2010 Elsevier Inc. All rights reserved.
- ItemSomente MetadadadosNitric oxide modulates metalloproteinase-2, collagen deposition and adhesion rate after polypropylene mesh implantation in the intra-abdominal wall(Elsevier B.V., 2012-01-01) Moretti, Ana I. S.; Souza Pinto, Francisco J. P.; Cury, Vivian; Jurado, Marcia C.; Marcondes, Wagner [UNIFESP]; Velasco, Irineu T.; Souza, Heraldo P.; Universidade de São Paulo (USP); Universidade Federal de São Paulo (UNIFESP)Prosthetic meshes are commonly used to correct abdominal wall defects. However, the inflammatory reaction induced by these devices in the peritoneum is not completely understood. We hypothesized that nitric oxide (NO), produced by nitric oxide synthase 2 (NOS2) may modulate the response induced by mesh implants in the abdominal wall and, consequently, affect the outcome of the surgical procedure. Polypropylene meshes were implanted in the peritoneal side of the abdominal wall in wild-type and NOS2-deficient (NOS2(-/-)) mice. After 15 days tissues around the mesh implant were collected, and inflammatory markers (the cytokine interleukin 1 beta (IL-1 beta) and NO) and tissue remodeling (collagen and metalloproteinases (MMP) 2 and 9) were analyzed. the lack of NOS2-derived NO induced a higher incidence of visceral adhesions at the mesh implantation site compared with wild-type mice that underwent the same procedure (P < 0.05). Additionally, higher levels of IL-1 beta were present in the mesh-implanted NOS2(-/-) animals compared with control and wild-type mice. Mesh implantation induced collagen I and III deposition, but in smaller amounts in NOS2(-/-) mice. MMP-9 activity after the surgical procedure was similarly increased in both groups. Conversely, MMP-2 activity was unchanged in mesh-implanted wild-type mice, but was significantly increased in NOS2(-/-) mice (P < 0.01), due to decreased S-nitrosylation of the enzyme in these animals. We conclude that NOS2-derived NO is crucial for an adequate response to and integration of polypropylene mesh implants in the peritoneum. NO deficiency results in a prolonged inflammatory reaction to the mesh implant, and reduced collagen deposition may contribute to an increased incidence of visceral adhesions. (C) 2011 Acta Materialia Inc. Published by Elsevier B.V. All rights reserved.
- ItemSomente MetadadadosStrategies to prevent hydrolytic degradation of the hybrid layer-A review(Elsevier B.V., 2013-10-01) Tjaderhane, Leo; Nascimento, Fabio D.; Breschi, Lorenzo; Mazzoni, Annalisa; Tersariol, Ivarne L. S. [UNIFESP]; Geraldeli, Saulo; Tezvergil-Mutluay, Arzu; Carrilho, Marcela; Carvalho, Ricardo M.; Tay, Franklin R.; Pashley, David H.; Univ Oulu; Univ Turku; NordicInst Dent Mat NIOM; Biomat Res Grp UNIBAN; Univ Trieste; IGM CNR; Univ Mogi das Cruzes; Universidade Federal de São Paulo (UNIFESP); Univ Florida; Univ Western Ontario; Univ British Columbia; Med Coll GeorgiaObjective. Endogenous dentin collagenolytic enzymes, matrix metalloproteinases (MMPs) and cysteine cathepsins, are responsible for the time-dependent hydrolysis of collagen matrix of hybrid layers. As collagen matrix integrity is essential for the preservation of long-term dentin bond strength, inhibition of endogenous dentin proteases is necessary for durable resin-bonded restorations.Methods. Several tentative approaches to prevent enzyme function have been proposed. Some of them have already demonstrated clinical efficacy, while others need to be researched further before clinical protocols can be proposed. This review will examine both the principles and outcomes of techniques to prevent collagen hydrolysis in dentin-resin interfaces.Results. Chlorhexidine, a general inhibitor of MMPs and cysteine cathepsins, is the most tested method. in general, these experiments have shown that enzyme inhibition is a promising approach to improve hybrid layer preservation and bond strength durability. Other enzyme inhibitors, e. g. enzyme-inhibiting monomers, may be considered promising alternatives that would allow more simple clinical application than chlorhexidine. Crosslinking collagen and/or dentin matrix-bound enzymes could render hybrid layer organic matrices resistant to degradation. Alternatively, complete removal of water from the hybrid layer with ethanol wet bonding or biomimetic remineralization should eliminate hydrolysis of both collagen and resin components.Significance. Understanding the function of the enzymes responsible for the hydrolysis of hybrid layer collagen has prompted several innovative approaches to retain hybrid layer integrity and strong dentin bonding. the ultimate goal, prevention of collagen matrix degradation with clinically applicable techniques and commercially available materials may be achievable in several ways. (C) 2013 Academy of Dental Materials. Published by Elsevier B.V. All rights reserved.