Endothelial signaling and the molecular basis of arteriovenous malformation |
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Authors: | Deepak Atri Bruno Larrivée Anne Eichmann Michael Simons |
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Affiliation: | 1. Section of Cardiovascular Medicine, Department of Internal Medicine, Yale Cardiovascular Research Center, Yale University School of Medicine, 333 Cedar St, New Haven, CT, 06510, USA 2. Department of Ophthalmology, H?pital Maisonneuve-Rosemont Research Centre, University of Montreal, Montreal, Canada 3. Center for Interdisciplinary Research in Biology (CIRB), Collège de France, Paris, France 4. Department of Cell Biology, Yale University School of Medicine, New Haven, USA
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Abstract: | Arteriovenous malformations occur when abnormalities of vascular patterning result in the flow of blood from arteries to veins without an intervening capillary bed. Recent work has revealed the importance of the Notch and TGF-β signaling pathways in vascular patterning. Specifically, Notch signaling has an increasingly apparent role in arterial specification and suppression of branching, whereas TGF-β is implicated in vascular smooth muscle development and remodeling under angiogenic stimuli. These physiologic roles, consequently, have implicated both pathways in the pathogenesis of arteriovenous malformation. In this review, we summarize the studies of endothelial signaling that contribute to arteriovenous malformation and the roles of genes implicated in their pathogenesis. We further discuss how endothelial signaling may contribute to vascular smooth muscle development and how knowledge of signaling pathways may provide us targets for medical therapy in these vascular lesions. |
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