Search: onr:"swepub:oai:DiVA.org:uu-259652" >
Sulindac metabolite...
Sulindac metabolites decrease cerebrovascular malformations in CCM3-knockout mice
-
Bravi, Luca (author)
-
Rudini, Noemi (author)
-
Cuttano, Roberto (author)
-
show more...
-
Giampietro, Costanza (author)
-
Maddaluno, Luigi (author)
-
Ferrarini, Luca (author)
-
Adams, Ralf H. (author)
-
Corada, Monica (author)
-
Boulday, Gwenola (author)
-
Tournier-Lasserve, Elizabeth (author)
-
- Dejana, Elisabetta (author)
- Uppsala universitet,Vaskulärbiologi
-
Lampugnani, Maria Grazia (author)
-
show less...
-
(creator_code:org_t)
- 2015-06-24
- 2015
- English.
-
In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 112:27, s. 8421-8426
- Related links:
-
https://www.pnas.org...
-
show more...
-
https://urn.kb.se/re...
-
https://doi.org/10.1...
-
show less...
Abstract
Subject headings
Close
- Cerebral cavernous malformation (CCM) is a disease of the central nervous system causing hemorrhage-prone multiple lumen vascular malformations and very severe neurological consequences. At present, the only recommended treatment of CCM is surgical. Because surgery is often not applicable, pharmacological treatment would be highly desirable. We describe here a murine model of the disease that develops after endothelial-cell-selective ablation of the CCM3 gene. We report an early, cell-autonomous, Wnt-receptor-independent stimulation of beta-catenin transcription activity in CCM3-deficient endothelial cells both in vitro and in vivo and a triggering of a beta-catenin-driven transcription program that leads to endothelial-tomesenchymal transition. TGF-beta/BMP signaling is then required for the progression of the disease. We also found that the anti-inflammatory drugs sulindac sulfide and sulindac sulfone, which attenuate beta-catenin transcription activity, reduce vascular malformations in endothelial CCM3-deficient mice. This study opens previously unidentified perspectives for an effective pharmacological therapy of intracranial vascular cavernomas.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Annan medicin och hälsovetenskap -- Övrig annan medicin och hälsovetenskap (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Other Medical and Health Sciences -- Other Medical and Health Sciences not elsewhere specified (hsv//eng)
Keyword
- cerebral cavernous malformation
- endothelial cells
- beta-catenin
- sulindac metabolites
- vascular pathology
Publication and Content Type
- ref (subject category)
- art (subject category)
Find in a library
To the university's database
- By the author/editor
-
Bravi, Luca
-
Rudini, Noemi
-
Cuttano, Roberto
-
Giampietro, Cost ...
-
Maddaluno, Luigi
-
Ferrarini, Luca
-
show more...
-
Adams, Ralf H.
-
Corada, Monica
-
Boulday, Gwenola
-
Tournier-Lasserv ...
-
Dejana, Elisabet ...
-
Lampugnani, Mari ...
-
show less...
- About the subject
-
- MEDICAL AND HEALTH SCIENCES
-
MEDICAL AND HEAL ...
-
and Other Medical an ...
-
and Other Medical an ...
- Articles in the publication
-
Proceedings of t ...
- By the university
-
Uppsala University