Artery smooth muscle- and vein smooth muscle-specific...

A - Human Necessities – 61 – K

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A61K 48/00 (2006.01) C12N 5/077 (2010.01) A01K 67/027 (2006.01) A61K 47/48 (2006.01) C07K 14/705 (2006.01) C12Q 1/00 (2006.01) C12Q 1/68 (2006.01) G01N 33/53 (2006.01) G01N 33/68 (2006.01)

Patent

CA 2429460

Arterial and venous smooth muscle cells are molecularly distinct from the earliest stages of angiogenesis through to adulthood. This distinction is revelated by expression on arterial cells (e.g., arterial endothelial cells, arterial smooth muscle cells) of a transmembrane ligand, called EphrinB2 whose receptor EphB4 is expressed on venous cells. Targeted disruption of the EphrinB2 genne prevents the remodeling of veins from a capillary plexus into properly branched structures. Moreover, it also disrupts the remodeling of arteries, suggesting that reciprocal interactions between pre-specified arterial and venous cells are necessary for angiogenesis. Expression of EphrinB2 in arterial cells (e.g., arterial endothelial cells, arterial smooth muscle cells) can be used to advantage in methods for targeting agents and/or encoded polypeptides to arterial smooth muscle cells, altering angiogenesis, assessing the effect of agents on arterial smooth muscle cells, identifying arterial smooth muscle cells, isolating arterial smooth muscle cells and production of artificial vessels, for example.

Les cellules de muscle lisse artérielles et veineuses sont différentes d'un point de vue moléculaire, depuis les premières étapes de l'angiogenèse jusqu'à l'état adulte. Cette différence est révélée par l'expression sur des cellules artérielles (telles que des cellules endothéliales artérielles, des cellules de muscle lisse artérielles) d'un ligand transmembranaire appelé EphrinB2, dont le récepteur EphB4 est exprimé sur des cellules veineuses. L'interruption ciblée du gène d'EphrinB2 empêche le remodelage de veines d'un plexus capillaire en structures correctement ramifiées. De plus, il interrompt également le remodelage d'artères, ce qui suggère que des interactions réciproques entre des cellules artérielles et veineuses précisées auparavant sont nécessaires à l'angiogenèse. L'expression d'EphrinB2 dans des cellules artérielles (telles que des cellules endothéliales artérielles, des cellules de muscle lisse artérielles) peut être avantageusement utilisée dans des procédés permettant de cibler des agents et/ou des polypeptides codés sur des cellules de muscle lisse artérielles, de modifier l'angiogenèse, d'évaluer l'effet d'agents sur des cellules de muscle lisse artérielles, d'identifier des cellules de muscle lisse artérielles, d'isoler des cellules de muscle lisse artérielles et de produire des vaisseaux artificiels, par exemple.

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