Publications by authors named "Joana Amado-Azevedo"

Article Synopsis
  • During inflammation, increased vascular permeability can lead to harmful effects, especially in inflamed lungs, where microvascular leakage occurs.
  • Formylated peptides, which trigger neutrophil activation through FPR1, play a role in regulating this vascular leakage, with research identifying ARAP3 as a protective factor against excessive permeability.
  • Studies showed that ARAP3 deficiency in endothelial and immune cells led to increased microvascular leakage and neutrophil activity, hinting at its significance in conditions with high levels of formylated peptides, such as severe influenza.
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Article Synopsis
  • Endothelial barrier disruption plays a crucial role in organ dysfunction during inflammatory conditions like sepsis, and the kinase Arg/Abl2 has been identified as a key mediator of this disruption.
  • Depleting Arg in endothelial cells activates RhoA and Rac1, enhancing cell adhesion and reducing cell retraction and gap formation.
  • Genetic deletion of Arg in vivo reduces vascular leaks in the skin and lungs, highlighting its importance as a potential therapeutic target for conditions associated with vascular leakage.
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Thrombin and other inflammatory mediators may induce vascular permeability through the disruption of adherens junctions between adjacent endothelial cells. If uncontrolled, hyperpermeability leads to an impaired barrier, fluid leakage and edema, which can contribute to multi-organ failure and death. RhoGTPases control cytoskeletal dynamics, adhesion and migration and are known regulators of endothelial integrity.

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Endothelial colony-forming cells (ECFC) are grown from circulating CD34(+) progenitors present in adult peripheral blood, but during in vitro expansion part of the cells lose CD34. To evaluate whether the regulation of CD34 characterizes the angiogenic phenotypical features of PB-ECFCs, we investigated the properties of CD34(+) and CD34(-) ECFCs with respect to their ability to form capillary-like tubes in 3D fibrin matrices, tip-cell gene expression, and barrier integrity. Selection of CD34(+) and CD34(-) ECFCs from subcultured ECFCs was accomplished by magnetic sorting (FACS: CD34(+): 95 % pos; CD34(-): 99 % neg).

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Although the endothelium is an extremely thin single-cell layer, it performs exceedingly well in preventing blood fluids from leaking into the surrounding tissues. However, specific pathological conditions can affect this cell layer, compromising the integrity of the barrier. Vascular leakage is a hallmark of many cardiovascular diseases and despite its medical importance, no specialized therapies are available to prevent it or reduce it.

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