Targeting beta 1-integrin inhibits vascular leakage in endotoxemia
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Authors: Hakanpaa, Laura; Kiss, Elina A.; Jacquemet, Guillaume; Miinalainen, Ilkka; Lerche, Martina; Guzman, Camilo; Mervaala, Eero; Eklund, Lauri; Ivaska, Johanna; Saharinen, Pipsa
Abstract
Loss of endothelial integrity promotes capillary leakage in numerous diseases, including sepsis, but there are no effective therapies for preserving endothelial barrier function. Angiopoietin-2 (ANGPT2) is a context-dependent regulator of vascular leakage that signals via both endothelial TEK receptor tyrosine kinase (TIE2) and integrins. Here, we show that antibodies against beta 1-integrin decrease LPS-induced vascular leakage in murine endotoxemia, as either a preventative or an intervention therapy. beta 1-integrin inhibiting antibodies bound to the vascular endotheliumin vivo improved the integrity of endothelial cell-cell junctions and protected mice from endotoxemia-associated cardiac failure, without affecting endothelial inflammation, serum proinflammatory cytokine levels, or TIE receptor signaling. Moreover, conditional deletion of a single allele of endothelial beta 1-integrin protected mice from LPS-induced vascular leakage. In endothelial mono-layers, the inflammatory agents thrombin, lipopolysaccharide (LPS), and IL-1 beta decreased junctional vascular endothelial (VE)-cadherin and induced actin stress fibers via beta 1- and alpha 5-integrins and ANGPT2. Additionally, beta 1-integrin inhibiting antibodies prevented inflammation-induced endothelial cell contractility and monolayer permeability. Mechanistically, the inflammatory agents stimulated ANGPT2-dependent translocation of alpha 5 beta 1-integrin into tensin-1-positive fibrillar adhesions, which destabilized the endothelial monolayer. Thus, beta 1-integrin promotes endothelial barrier disruption during inflammation, and targeting beta 1-integrin signaling could serve as a novel means of blocking pathological vascular leak.
Highly active platinum supported on Mo-doped titanium nanotubes suboxide (Pt/TNTS-Mo) electrocatalyst for oxygen reduction reaction in PEMFC
RENEWABLE ENERGY
Authors: Esfahani, Reza Alipour Moghadam; Rivera Gavidia, Luis Miguel; Garcia, Gonzalo; Pastor, Elena; Specchia, Stefania
Abstract
In this study, an innovative carbon-free electrocatalyst for oxygen reduction reaction was synthesized via deposition of platinum on titanium nanotube suboxide (trititanium pentoxide nanotubes, TNTS) obtained from titania doped with molybdenum (Pt/TNTS-Mo). The TNTS-Mo support was synthesized in autoclave, while the Pt/TNTS-Mo using the polyol method. The carbon-free support and the Pt-based catalyst were fully characterized via rotating disk electrode (RDE) technique and polymer exchange membrane fuel cell (PEMFC) station by preparing a membrane electrode assembly (MEA) with Nafion (R) 115, loaded with 0.35 mg(pt) cm(-2) of Pt/TNTS-Mo at the cathode, and 035 mgpt cm-2 of commercial Pt/C (E-TEK) at the anode. In RDE experiments, the Pt/TNTS-Mo exhibited low overpotential and remarkable electroactivity toward oxygen reduction reaction (ORR: mass activity of 110.7 mA mg(Pt)(-1) at 0.9 V vs SHE). Moreover, the Pt/TNTS-Mo demonstrated excellent stability. Tests in a 25 cm(2) single cell PEMFC resulted to maximum power density of 0.52 W cm(-2). (C) 2017 Elsevier Ltd. All rights reserved.