Skip to Main content Skip to Navigation
Journal articles

Trans-arachidonic acids generated during nitrative stress induce a thrombospondin-1-dependent microvascular degeneration.

Abstract : Nitrative stress has an important role in microvascular degeneration leading to ischemia in conditions such as diabetic retinopathy and retinopathy of prematurity. Thus far, mediators of nitrative stress have been poorly characterized. We recently described that trans-arachidonic acids are major products of NO(2)(*)-mediated isomerization of arachidonic acid within the cell membrane, but their biological relevance is unknown. Here we show that trans-arachidonic acids are generated in a model of retinal microangiopathy in vivo in a NO(*)-dependent manner. They induce a selective time- and concentration-dependent apoptosis of microvascular endothelial cells in vitro, and result in retinal microvascular degeneration ex vivo and in vivo. These effects are mediated by an upregulation of the antiangiogenic factor thrombospondin-1, independently of classical arachidonic acid metabolism. Our findings provide new insight into the molecular mechanisms of nitrative stress in microvascular injury and suggest new therapeutic avenues in the management of disorders involving nitrative stress, such as ischemic retinopathies and encephalopathies.
Document type :
Journal articles
Complete list of metadatas

https://www.hal.inserm.fr/inserm-00150825
Contributor : Florian Sennlaub <>
Submitted on : Thursday, May 31, 2007 - 4:24:43 PM
Last modification on : Wednesday, September 23, 2020 - 4:34:37 AM
Long-term archiving on: : Friday, November 25, 2016 - 4:01:14 PM

File

 Restricted access
To satisfy the distribution rights of the publisher, the document is embargoed until : jamais

Please log in to resquest access to the document

Identifiers

Collections

Citation

Elsa Kermorvant-Duchemin, Florian Sennlaub, Mirna Sirinyan, Sonia Brault, Gregor Andelfinger, et al.. Trans-arachidonic acids generated during nitrative stress induce a thrombospondin-1-dependent microvascular degeneration.. Nature Medicine, Nature Publishing Group, 2005, 11 (12), pp.1339-45. ⟨10.1038/nm1336⟩. ⟨inserm-00150825⟩

Share

Metrics

Record views

311