TY  - JOUR
A1  - Weißmann, Norbert
A1  - Sydykov, Akylbek
A1  - Kalwa, Hermann
A1  - Storch, Ursula
A1  - Fuchs, Beate
A1  - Mederos y Schnitzler, Michael
A1  - Brandes, Ralf
A1  - Grimminger, Friedrich
A1  - Meissner, Marcel
A1  - Freichel, Marc
A1  - Offermanns, Stefan
A1  - Veit, Florian
A1  - Pak, Oleg
A1  - Krause, Karl-Heinz
A1  - Schermuly, Ralph T.
A1  - Brewer, Alison C.
A1  - Schmidt, Harald H. H. W.
A1  - Seeger, Werner
A1  - Shah, Ajay M.
A1  - Gudermann, Thomas
A1  - Ghofrani, Hossein A.
A1  - Dietrich, Alexander
T1  - Activation of TRPC6 channels is essential for lung ischaemia–reperfusion induced oedema in mice
T2  - Nature Communications
N2  - Lung ischaemia–reperfusion-induced oedema (LIRE) is a life-threatening condition that causes pulmonary oedema induced by endothelial dysfunction. Here we show that lungs from mice lacking nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox2y/−) or the classical transient receptor potential channel 6 (TRPC6−/−) are protected from LIR-induced oedema (LIRE). Generation of chimeric mice by bone marrow cell transplantation and endothelial-specific Nox2 deletion showed that endothelial Nox2, but not leukocytic Nox2 or TRPC6, are responsible for LIRE. Lung endothelial cells from Nox2- or TRPC6-deficient mice showed attenuated ischaemia-induced Ca2+ influx, cellular shape changes and impaired barrier function. Production of reactive oxygen species was completely abolished in Nox2y/− cells. A novel mechanistic model comprising endothelial Nox2-derived production of superoxide, activation of phospholipase C-γ, inhibition of diacylglycerol (DAG) kinase, DAG-mediated activation of TRPC6 and ensuing LIRE is supported by pharmacological and molecular evidence. This mechanism highlights novel pharmacological targets for the treatment of LIRE.
Y1  - 2012
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/25802
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-258020
SN  - 2041-1723
VL  - 3
IS  - 649
PB  - Nature Publishing Group
CY  - London
ER  -