INTRODUCTION: Excessive vascular permeability is a characteristic feature of ALI. We have previously demonstrated that UFH prevents LPS-induced disruption of endothelial barrier function in vitro. It was the objective of this study to determine whether UFH may attenuate endotoxin-induced lung vascular leak in mice and to further explore the possible underlying mechanisms. METHODS: C57BL/6J mice were randomly divided into the control, LPS and LPS plus UFH groups. Sepsis was induced by intraperitoneal injection of LPS at a dose of 30 mg/kg. Mice in the LPS plus UFH group were intravenously received 8 units UFH (heparin sodium) diluted in 20 μl sterile saline at 0.5 h before the injection of LPS. RESULTS: 1) UFH pretreatment attenuated LPS-induced histopathological changes in Lung at 6 h; 2) Pretreatment of mice with UFH ameliorated LPS-induced lung edema and lung vascular leak at 6 h; 3) UFH pretreatment dramatically inhibited RhoA and ROCK activation in the lung tissues of LPS-treated mice (3 and 6 h). 4) UFH pretreatment significantly down-regulated ROCK1 gene expression, but did not affect the increased expression of ROCK2 mRNA in the lung tissues of LPS-treated mice at 3 or 6 h. CONCLUSION: These data suggest that UFH may attenuate endotoxin-induced lung vascular leak by regulating RhoA/Rho kinase pathway.
INTRODUCTION: Excessive vascular permeability is a characteristic feature of ALI. We have previously demonstrated that UFH prevents LPS-induced disruption of endothelial barrier function in vitro. It was the objective of this study to determine whether UFH may attenuate endotoxin-induced lung vascular leak in mice and to further explore the possible underlying mechanisms. METHODS: C57BL/6J mice were randomly divided into the control, LPS and LPS plus UFH groups. Sepsis was induced by intraperitoneal injection of LPS at a dose of 30 mg/kg. Mice in the LPS plus UFH group were intravenously received 8 units UFH (heparin sodium) diluted in 20 μl sterile saline at 0.5 h before the injection of LPS. RESULTS: 1) UFH pretreatment attenuated LPS-induced histopathological changes in Lung at 6 h; 2) Pretreatment of mice with UFH ameliorated LPS-induced lung edema and lung vascular leak at 6 h; 3) UFH pretreatment dramatically inhibited RhoA and ROCK activation in the lung tissues of LPS-treated mice (3 and 6 h). 4) UFH pretreatment significantly down-regulated ROCK1 gene expression, but did not affect the increased expression of ROCK2 mRNA in the lung tissues of LPS-treated mice at 3 or 6 h. CONCLUSION: These data suggest that UFH may attenuate endotoxin-induced lung vascular leak by regulating RhoA/Rho kinase pathway.
Authors: Michael Schnoor; Alexander García Ponce; Eduardo Vadillo; Rosana Pelayo; Jan Rossaint; Alexander Zarbock Journal: Cell Mol Life Sci Date: 2017-02-02 Impact factor: 9.261
Authors: Ryan J Good; Laura Hernandez-Lagunas; Ayed Allawzi; Joanne K Maltzahn; Christine U Vohwinkel; Arun K Upadhyay; Uday B Kompella; Konstantin G Birukov; Todd C Carpenter; Carmen C Sucharov; Eva Nozik-Grayck Journal: Am J Physiol Lung Cell Mol Physiol Date: 2018-07-19 Impact factor: 5.464
Authors: Sara Lynn N Farwell; Daniela Kanyi; Marianne Hamel; Joshua B Slee; Elizabeth A Miller; Mark D Cipolle; Linda J Lowe-Krentz Journal: J Biol Chem Date: 2016-01-14 Impact factor: 5.157