Control of a gene induced by oxidized lipids in human artery...

C - Chemistry – Metallurgy – 12 – Q

Patent

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C12Q 1/68 (2006.01) A61K 48/00 (2006.01) C07H 21/02 (2006.01) C07H 21/04 (2006.01) C12Q 1/42 (2006.01) G01N 33/53 (2006.01) G01N 33/573 (2006.01) G01N 33/92 (2006.01)

Patent

CA 2404350

This invention provides novel methods of inhibiting one or more symptoms of atherosclerosis. Also provided are assays for compounds that will inhibit the progression and/or ameliorate one or more symptoms of atherosclerosis. The methods and assays are based, in part, on the discovery that oxidized LDL or components thereof induce strong upregulation of MAP kinase phosphatase-1 which, in turn, is associated with an "inflammatory response" characteristic of atherosclerotic plaque formation. Inhibition of MKP-1 inhibits one or more symptoms of this response, e.g. monocyte adhesion, monocyte chemotaxis, differentiation into macrophages,etc. Inhibition of MKP-1 thus provides an effective method of inhibiting symptoms of atherosclerosis.

L'invention concerne de nouveaux procédés visant à inhiber un ou plusieurs symptômes d'athérosclérose. L'invention concerne aussi des techniques de détection de composés inhibant la progression et/ou améliorant un ou plusieurs symptômes d'athérosclérose. Les procédés et les titrages se basent en partie sur la découverte selon laquelle les LDL oxydées ou des constituants de celles-ci induisent une forte régulation positive de MAP kinase phosphatase 1, qui, à son tour, est associée à une caractéristique de <= réaction inflammatoire >= de formation de plaques athéroscléreuses. L'inhibition de MKP-1 inhibe un ou plusieurs symptômes de cette réaction, p. ex. l'adhésion des monocytes, la chimiotaxie des monocytes, la différenciation en macrophages, etc. L'inhibition de MKP-1 constitue ainsi un procédé efficace d'inhibition des symptômes d'athérosclérose.

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