Refine
Year of publication
Document Type
- Article (35)
- Preprint (14)
- diplomthesis (1)
- Doctoral Thesis (1)
Has Fulltext
- yes (51) (remove)
Is part of the Bibliography
- no (51)
Keywords
- LHC (3)
- ALICE (2)
- Podospora anserina (2)
- aging (2)
- mitochondria (2)
- 900 GeV (1)
- ACLF (1)
- ADHD (1)
- Atoms (1)
- Buprestidae (1)
Institute
- Physik (28)
- Frankfurt Institute for Advanced Studies (FIAS) (24)
- Informatik (24)
- Medizin (14)
- Geowissenschaften (4)
- Biowissenschaften (2)
- ELEMENTS (2)
- Mathematik (1)
- Pharmazie (1)
Activation of TRPC6 channels is essential for lung ischaemia–reperfusion induced oedema in mice
(2012)
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.