Trans-arachidonic acids generated during nitrative stress induce a thrombospondin-1–dependent microvascular degeneration View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2005-11-27

AUTHORS

Elsa Kermorvant-Duchemin, Florian Sennlaub, Mirna Sirinyan, Sonia Brault, Gregor Andelfinger, Amna Kooli, Stéphane Germain, Huy Ong, Pedro d'Orleans-Juste, Fernand Gobeil, Tang Zhu, Chantal Boisvert, Pierre Hardy, Kavita Jain, J Russel Falck, Michael Balazy, Sylvain Chemtob

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 NO2•-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. More... »

PAGES

1339-1345

Journal

TITLE

Nature Medicine

ISSUE

12

VOLUME

11

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nm1336

DOI

http://dx.doi.org/10.1038/nm1336

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1034420089

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/16311602


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350 schema:name Department of Pediatrics, Ophthalmology and Pharmacology, Research Center, Hôpital Ste-Justine, 3175 Côte de Ste-Catherine, H3T1C5, Montréal, Québec, Canada
351 Inserm, Unité 598, Institut Biomédical des Cordeliers, 75006, Paris, France
352 rdf:type schema:Organization
353 grid-institutes:grid.7429.8 schema:alternateName Inserm, Unité 36, Collège de France, 75006, Paris, France
354 schema:name Inserm, Unité 36, Collège de France, 75006, Paris, France
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356 grid-institutes:grid.86715.3d schema:alternateName Department of Pharmacology, Université de Sherbrooke, 3001 12e Avenue Nord Sherbrooke, J1K2R1, Quebec, Canada
357 schema:name Department of Pharmacology, Université de Sherbrooke, 3001 12e Avenue Nord Sherbrooke, J1K2R1, Quebec, Canada
358 rdf:type schema:Organization
 




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