VE-cadherin-mediated cell-cell junction weakening increases paracellular permeability in response to both angiogenic and inflammatory stimuli. Although Semaphorin 3A has emerged as one of the few known anti-angiogenic factors to exhibit pro-permeability activity, little is known about how it triggers vascular leakage. Here we report that Semaphorin 3A induced VE-cadherin serine phosphorylation ...

The growth factor angiopoietin-1 (Ang1) has been identified as the primary activating ligand for Tie2, a tyrosine kinase receptor highly expressed in vascular endothelial cells. Genetic studies using targeted mutations in mice have demonstrated that Tie2 activation by Ang1 is crucial for angiogenesis, vascular remodelling, and vascular maturation. However, the angiogenic functions of Ang1 are d...

The endothelial barrier strictly maintains vascular and tissue homeostasis, and therefore modulates many physiological processes such as angiogenesis, immune responses, and dynamic exchanges throughout organs. Consequently, alteration of this finely tuned function may have devastating consequences for the organism. This is particularly obvious in cancers, where a disorganized and leaky blood ve...

Hantaviruses cause two vascular permeability-based diseases and primarily infect endothelial cells which form the primary fluid barrier of the vasculature. Since hantavirus infections are not lytic, the mechanisms by which hantaviruses cause haemorrhagic fever with renal syndrome (HFRS) or Hantavirus Pulmonary Syndrome (HPS) are indeterminate. HPS is associated with acute pulmonary oedema and H...

OBJECTIVE The molecular mechanisms regulating vascular permeability are only now being elucidated. The junctional adhesion molecule (JAM) JAM-C has been linked to the induction of vascular permeability. We sought to understand the mechanism whereby JAM-C may disrupt junctional integrity in endothelial cells (ECs). METHODS AND RESULTS We show here that JAM-C alters permeability through modulat...

Vascular endothelial growth factor (VEGF) promotes angiogenesis by a variety of mechanisms including stimulation of endothelial cell proliferation and migration and increasing vascular permeability. Although its mitogenic activity is mediated primarily by the beta(2)-isoforms of protein kinase C (PKC), little is known about the signaling pathways transducing its other physiological properties. ...

We developed a microfluidic model of microcirculation containing both blood and lymphatic vessels for examining vascular permeability. The designed microfluidic device harbors upper and lower channels that are partly aligned and are separated by a porous membrane, and on this membrane, blood vascular endothelial cells (BECs) and lymphatic endothelial cells (LECs) were cocultured back-to-back. A...

RANKL is emerging as an important regulator of vascular pathophysiology. We here demonstrate a novel role of RANKL as a vascular permeability factor, and a critical role of endothelial nitric oxide synthase (eNOS), in RANKL-induced endothelial function. RANKL increased the vascular permeability and leukocyte infiltration in vivo and caused the breakdown of the blood-retinal barrier in wild type...

OBJECTIVES To evaluate the diagnostic value of plasma protein levels for pulmonary vascular permeability and acute respiratory distress syndrome. During acute lung injury and acute respiratory distress syndrome, increased vascular permeability induces protein-rich fluid extravasation. We hypothesized that plasma protein levels predict increased vascular permeability and acute respiratory distre...

Massive burn trauma is characterized by hypovolemic shock induced by the loss of plasma from vessels. The elevation of vascular permeability and the ultimate formation of tissue edema are important events during the development of severe burn injury. The underlying mechanisms involved in the increased permeability include the activation of multiple endothelial signaling pathways and the changes...