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Acta Physiologica 2012; Volume 204, Supplement 689
91st Annual Meeting of The German Physiological Society
3/22/2012-3/25/2012
Dresden, Germany
NOTCH SIGNALLING IS ESSENTIAL TO MAINTAIN VASCULAR INTEGRITY
Abstract number: O135
Fischer1 *A., Adam1 G., Liebler1 S., Wustehube1 J.
1Medizinische Fakultt Mannheim & DKFZ Heidelberg, Vaskulre Biologie, Mannheim, Germany
Question:
Blood vessels in the central nervous system are more than bystanders that only react to the needs of neural cells. Several genetic diseases have highlighted that disturbed vascular functions can be the principle cause for neurological disorders. We have shown recently that loss of CCM1 (KRIT1) induces angiogenesis and causes the formation of cerebral cavernous malformations. This is mediated by unbalanced Rho kinase activity, AKT and Notch signalling. The Delta-Notch cascade is essential for cardiovascular development and controls arteriovenous differentiation and sprouting angiogenesis. The roles of this pathway for blood vessel physiology in the adult are poorly understood.
Methods:
We present gain and loss-of-function approaches in primary human endothelial cells and pericytes as well as in transgenic mouse lines.
Results:
The data suggest that Notch signalling is essential for vascular maintenance in the adult. This pathway is needed to prevent uncontrolled angiogenesis and to protect vascular barrier functions. Additionally, Notch signalling in endothelial cells and pericytes regulates cell contraction as well as adhesive properties. This has implications for permeability control, cellular extravasation and vascular tone.
Conclusions:
Notch signals are not only needed to shape the vascular system during growth and development but also to maintain vascular integrity and function during adulthood.
To cite this abstract, please use the following information:
Acta Physiologica 2012; Volume 204, Supplement 689 :O135