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    Endothelial MMP-9 Drives the Inflammatory Response in Abdominal Aortic Aneurysm (AAA)

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    Abdominal aortic aneurysm (AAA) is a complex multi-factorial disease leading to life-threatening complications. Chronic inflammation and extracellular matrix degradation are the major pathological features of AAA. Vascular inflammation involves complex interaction among inflammatory cells (i.e. neutrophils, lymphocytes, monocytes, macrophages), endothelial cells (ECs), vascular smooth muscle cells (VSMCs), and extracellular matrix (ECM). Although vascular endothelium plays a key role in aneurysm disease, the molecular mechanisms underlying its involvement is only partially understood. In this study, we have characterized the role of matrix matrix metalloproteinase-9 (MMP-9) as potential trigger of the inflammatory response during the reciprocal interaction between ECs and VSMCs. Briefly, in biopsies of human AAA we found increased level of MMP-9, IL-6 and monocyte chemoattractant protein-1 (MCP-1), which correlated with a massive medial neo-angiogenesis. In particular, in vitro silencing of MMP-9 in ECs, using specific shRNA delivered by lentiviral vectors, inhibited TNF-alpha mediated activation of NF-kB. In addition, ECS void of MMP-9 failed to migrate in 3D matrix and affected VSMC behavior in terms of matrix remodeling. Overall our findings indicate that silencing of MMP-9 may represent a therapeutic target to restore vascular extracellular matrix remodeling

    Biomechanically improved hybrid matrices: the effect of recombinant human elastin-like polypeptides (HELP) on collagen three-dimensional scaffolds

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    The replacement of diseased tissues with biological substitutes with suitable biomechanical properties is one of the most important goal in tissue engineering. Collagen represents a satisfactory choice for scaffolds. Unfortunately, the lack of elasticity represents a restriction to a wide use of collagen for several applications. In this work, we studied the effect of human elastin-like polypeptide (HELP) as hybrid collagen-elastin matrices. In particular, we studied the biomechanical properties of collagen/HELP scaffolds considering several components involved in ECM remodeling (elastin, collagen, fibrillin, lectin-like receptor, metalloproteinases) and cell phenotype (myogenin, myosin heavy chain) with particular awareness for vascular tissue engineering applications. Elastin and collagen content resulted upregulated in collagen-HELP matrices, even showing an improved structural remodeling through the involvement of proteins to a ECM remodeling activity. Moreover, the hybrid matrices enhanced the contractile activity of C2C12 cells concurring to improve the mechanical properties of the scaffold. Finally, small-angle X-ray scattering analyses were performed to enable a very detailed analysis of the matrices at the nanoscale, comparing the scaffolds with native blood vessels. In conclusion, our work shows the use of recombinant HELP, as a very promising complement able to significantly improve the biomechanical properties of three-dimensional collagen matrices in terms of tensile stress and elastic modulus
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