A method of modulating endothelial cell activity by...

C - Chemistry – Metallurgy – 12 – N

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C12N 15/12 (2006.01) A61K 38/45 (2006.01) A61K 48/00 (2006.01) C12N 5/16 (2006.01) C12N 9/12 (2006.01) C12N 15/63 (2006.01)

Patent

CA 2502257

The present invention relates generally to a method of modulating endothelial cell functional characteristics and to agents useful for same. More particularly, the present invention relates to a method of modulating vascular endothelial cell pro-inflammatory and angiogenic phenotypes by modulating the functional levels of intracellular sphingosine kinase. The method of the present invention is useful, inter alia, in relation to the treatment and/or prophylaxis of conditions which are characterised by inadequate endothelial cell functioning and may include conditions such as vascular engraftment, organ transplantation or wound healing or conditions which are characterised by an aberrant endothelial cell inflammatory or angiogenic phenotype. Further, the method of the present invention facilitates the development of agents, such as functionally manipulated endothelial cell populations, for a range of therapeutic and/or prophylactic uses.

La présente invention concerne d'une manière générale un procédé de modulation des caractéristiques fonctionnelles d'une cellule endothéliale ainsi que des agents servant à mettre en oeuvre ce procédé. Cette invention concerne en particulier un procédé de modulation des phénotypes pro-inflammatoire et angiogénique des cellules endothéliales vasculaires consistant à moduler les niveaux fonctionnels de sphingosine kinase intracellulaire. Le procédé de cette invention est utilisé, inter alia, dans le cadre du traitement et/ou de la prévention d'états qui se caractérisent par un mauvais fonctionnement des cellules endothéliales et qui peuvent comprendre la greffe vasculaire, la transplantation d'organe ou la cicatrisation des blessures ou d'états qui se caractérisent par un phénotype inflammatoire ou angiogénique aberrant des cellules endothéliales. Le procédé de la présente invention sert en outre à faciliter le développement d'agents tels que des populations de cellules endothéliales fonctionnellement manipulées en vue d'une gamme d'applications thérapeutiques et/ou prophylactiques.

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