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

Publication ,  Journal Article
Kermorvant-Duchemin, E; Sennlaub, F; Sirinyan, M; Brault, S; Andelfinger, G; Kooli, A; Germain, S; Ong, H; d'Orleans-Juste, P; Gobeil, F ...
Published in: Nature medicine
December 2005

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.

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Published In

Nature medicine

DOI

EISSN

1546-170X

ISSN

1078-8956

Publication Date

December 2005

Volume

11

Issue

12

Start / End Page

1339 / 1345

Related Subject Headings

  • Thrombospondin 1
  • Thiazoles
  • Tetrazolium Salts
  • Sus scrofa
  • Reverse Transcriptase Polymerase Chain Reaction
  • Retinal Vessels
  • Rats, Sprague-Dawley
  • Rats
  • Nitric Oxide
  • Neovascularization, Physiologic
 

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Kermorvant-Duchemin, E., Sennlaub, F., Sirinyan, M., Brault, S., Andelfinger, G., Kooli, A., … Chemtob, S. (2005). Trans-arachidonic acids generated during nitrative stress induce a thrombospondin-1-dependent microvascular degeneration. Nature Medicine, 11(12), 1339–1345. https://doi.org/10.1038/nm1336
Kermorvant-Duchemin, Elsa, Florian Sennlaub, Mirna Sirinyan, Sonia Brault, Gregor Andelfinger, Amna Kooli, Stéphane Germain, et al. “Trans-arachidonic acids generated during nitrative stress induce a thrombospondin-1-dependent microvascular degeneration.Nature Medicine 11, no. 12 (December 2005): 1339–45. https://doi.org/10.1038/nm1336.
Kermorvant-Duchemin E, Sennlaub F, Sirinyan M, Brault S, Andelfinger G, Kooli A, et al. Trans-arachidonic acids generated during nitrative stress induce a thrombospondin-1-dependent microvascular degeneration. Nature medicine. 2005 Dec;11(12):1339–45.
Kermorvant-Duchemin, Elsa, et al. “Trans-arachidonic acids generated during nitrative stress induce a thrombospondin-1-dependent microvascular degeneration.Nature Medicine, vol. 11, no. 12, Dec. 2005, pp. 1339–45. Epmc, doi:10.1038/nm1336.
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. Trans-arachidonic acids generated during nitrative stress induce a thrombospondin-1-dependent microvascular degeneration. Nature medicine. 2005 Dec;11(12):1339–1345.

Published In

Nature medicine

DOI

EISSN

1546-170X

ISSN

1078-8956

Publication Date

December 2005

Volume

11

Issue

12

Start / End Page

1339 / 1345

Related Subject Headings

  • Thrombospondin 1
  • Thiazoles
  • Tetrazolium Salts
  • Sus scrofa
  • Reverse Transcriptase Polymerase Chain Reaction
  • Retinal Vessels
  • Rats, Sprague-Dawley
  • Rats
  • Nitric Oxide
  • Neovascularization, Physiologic