22 research outputs found

    MVL-PLA2, a Snake Venom Phospholipase A2, Inhibits Angiogenesis through an Increase in Microtubule Dynamics and Disorganization of Focal Adhesions

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    Integrins are essential protagonists of the complex multi-step process of angiogenesis that has now become a major target for the development of anticancer therapies. We recently reported and characterized that MVL-PLA2, a novel phospholipase A2 from Macrovipera lebetina venom, exhibited anti-integrin activity. In this study, we show that MVL-PLA2 also displays potent anti-angiogenic properties. This phospholipase A2 inhibited adhesion and migration of human microvascular-endothelial cells (HMEC-1) in a dose-dependent manner without being cytotoxic. Using Matrigel™ and chick chorioallantoic membrane assays, we demonstrated that MVL-PLA2, as well as its catalytically inactivated form, significantly inhibited angiogenesis both in vitro and in vivo. We have also found that the actin cytoskeleton and the distribution of αvβ3 integrin, a critical regulator of angiogenesis and a major component of focal adhesions, were disturbed after MVL-PLA2 treatment. In order to further investigate the mechanism of action of this protein on endothelial cells, we analyzed the dynamic instability behavior of microtubules in living endothelial cells. Interestingly, we showed that MVL-PLA2 significantly increased microtubule dynamicity in HMEC-1 cells by 40%. We propose that the enhancement of microtubule dynamics may explain the alterations in the formation of focal adhesions, leading to inhibition of cell adhesion and migration

    Experimental and numerical analysis of reinforced stone block masonry beams using GFRP reinforcement

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    International audienceThis paper deals with an experimental and numerical study of stone block masonry beams externally reinforced using glass fiber-reinforced polymers (GFRP) strips. This study is conducted in order to investigate their flexural behavior. Eight masonry beams with 1.024 m span were loaded monotonically up to failure under four-point bending setup. All the tested beams have two courses of stone masonry units. Two unreinforced masonry beams were considered as the reference specimens. The remaining six beams were externally reinforced using hand-made GFRP strips with different layers of chopped glass strand mat (two, three and four layers).In the purpose to replicate ancient stone masonry structures, stone blocks were adopted and lime-based mortar was used to prepare beams. Typical load–displacement curves of the tested beams were compared and discussed.Finite element (FE) modelling analyses, considering the Drucker–Prager criterion, were performed using ABAQUS to predict ultimate loading capacity and the failure mode of the masonry beams. By comparing numerical results with experimental ones, over and above the effectiveness of GFRP strips as external strengthening for stone masonry beams, the proposed finite element model has been validated and can be used for numerical analysis of ancient masonry structures
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