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Bone marrow angiogenesis is increased in non-Hodgkin lymphomas (NHL). Compounds affecting extracellular matrix (ECM) may modify angiogenesis. Here we investigated ECM regulators in 48 unselected NHL patients compared with 35 controls. Untreated patients had elevated (P < 0.05) serum matrix metalloproteinase (MMP) 9 and tissue inhibitor of metalloproteinase (TIMP) 1, while MMP-2, TIMP-2 and syndecan-1 were not significantly different from controls. MMP-9 mRNA was significantly up-regulated in blood mononuclear cells, while mRNA expressions of the other ECM regulators were unaltered. We found strong correlations between mRNA expressions of both vascular endothelial growth factor and fibroblast growth factor 2, and MMP-9, TIMP-1 and TIMP-2. After therapy, serum MMP-2 increased while MMP-9 decreased (P < 0.05), the others being unchanged. Several compounds affecting ECM may be involved in angiogenic activity in NHL.

Background: Hyperglycaemia may contribute to endothelial dysfunction. Disturbances in endothelial functions include changes in the extracellular matrix underneath the cells. This may result from altered biosynthesis of matrix molecules or from modified biosynthesis and secretion of enzymes involved in the turnover of extracellular matrix. One important class of such enzymes are the matrix metalloproteinases (MMPs)., Aim of the Study: The aim of this study was to investigate whether the condition of high glucose concentration relevant both to diabetes type 1 and 2 and metabolic syndrome, would affect the synthesis and release of MMPs in human umbilical cord endothelial cells (HUVEC) in vitro., Methods: The HUVEC were isolated and cultured in vitro. The cells were exposed to medium with either low glucose (LG, 1 g/l) or high glucose (HG, 4.5 g/l) or the advanced glycation end product (AGE) N(epsilon)-(carboxymethyl) lysine bovine serum albumin (CML-BSA), at a concentration of 10 microg/ml. The HUVEC-conditioned media were harvested and subjected to gelatin zymography and Western blotting., Results: When HUVEC were incubated with HG or CML-BSA under serum free conditions a decreased secretion of pro MMP-2 was observed, both with gelatin zymography and Western blotting. The HUVEC also secreted MMP-9, but at lower levels, and effects of HG treatment were not significant. When HUVEC were stimulated with phorbol 12-myristate 13-acetate (PMA) secretion of pro MMP-2 was not increased, but the activation of pro MMP-2 into lower molecular forms increased, irrespective of culturing in LG, HG or CML-BSA., Conclusion: The HUVEC exposed to high glucose or AGE exhibit decreased secretion of MMP-2. These findings may be relevant in understanding the altered turnover of the endothelial extracellular matrix observed in the diabetic state.

Introduction: The skeletal muscle deformity of commercial chickens (Gallus gallus), known as the wooden breast (WB), is associated with fibrotic myopathy of unknown etiology. For future breeding strategies and genetic improvements, it is essential to identify the molecular mechanisms underlying the phenotype. The pathophysiological hallmarks of WB include severe skeletal muscle fibrosis, inflammation, myofiber necrosis, and multifocal degeneration of muscle tissue. The transmembrane proteoglycans syndecans have a wide spectrum of biological functions and are master regulators of tissue homeostasis. They are upregulated and shed (cleaved) as a regulatory mechanism during tissue repair and regeneration. During the last decades, it has become clear that the syndecan family also has critical functions in skeletal muscle growth, however, their potential involvement in WB pathogenesis is unknown. Methods: In this study, we have categorized four groups of WB myopathy in broiler chickens and performed a comprehensive characterization of the molecular and histological profiles of two of them, with a special focus on the role of the syndecans and remodeling of the extracellular matrix (ECM). Results and discussion: Our findings reveal differential expression and shedding of the four syndecan family members and increased matrix metalloproteinase activity. Additionally, we identified alterations in key signaling pathways such as MAPK, AKT, and Wnt. Our work provides novel insights into a deeper understanding of WB pathogenesis and suggests potential therapeutic targets for this condition. [ABSTRACT FROM AUTHOR]

Background Hyperglycaemia may contribute to endothelial dysfunction. Disturbances in endothelial functions include changes in the extracellular matrix underneath the cells. This may result from altered biosynthesis of matrix molecules or from modified biosynthesis and secretion of enzymes involved in the turnover of extracellular matrix. One important class of such enzymes are the matrix metalloproteinases (MMPs). Aim of the study The aim of this study was to investigate whether the condition of high glucose concentration relevant both to diabetes type 1 and 2 and metabolic syndrome, would affect the synthesis and release of MMPs in human umbilical cord endothelial cells (HUVEC) in vitro. Methods The HUVEC were isolated and cultured in vitro. The cells were exposed to medium with either low glucose (LG, 1 g/l) or high glucose (HG, 4.5 g/l) or the advanced glycation end product (AGE) Nε-(carboxymethyl) lysine bovine serum albumin (CMLBSA), at a concentration of 10 µg/ml. The HUVEC-conditioned media were harvested and subjected to gelatin zymography and Western blotting. Results When HUVEC were incubated with HG or CML-BSA under serum free conditions a decreased secretion of pro MMP-2 was observed, both with gelatin zymography and Western blotting. The HUVEC also secreted MMP-9, but at lower levels, and effects of HG treatment were not significant. When HUVEC were stimulated with phorbol 12-myristate 13-acetate (PMA) secretion of pro MMP-2 was not increased, but the activation of pro MMP-2 into lower molecular forms increased, irrespective of culturing in LG, HG or CML-BSA. Conclusion The HUVEC exposed to high glucose or AGE exhibit decreased secretion of MMP-2. These findings may be relevant in understanding the altered turnover of the endothelial extracellular matrix observed in the diabetic state. [ABSTRACT FROM AUTHOR]