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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Kermorvant-Duchemin, E; Sennlaub, F; Sirinyan, M; Brault, S; Andelfinger, G; Kooli, A; Germain, S; Ong, H; d'Orleans-Juste, P; Gobeil, F; Zhu, T; Boisvert, C; Hardy, P; Jain, K; Falck, JR; Balazy, M; Chemtob, S

Published Date

  • December 2005

Published In

Volume / Issue

  • 11 / 12

Start / End Page

  • 1339 - 1345

PubMed ID

  • 16311602

Pubmed Central ID

  • 16311602

International Standard Serial Number (ISSN)

  • 1078-8956

Digital Object Identifier (DOI)

  • 10.1038/nm1336

Language

  • eng

Conference Location

  • United States