Atri Deepak, Larrivée Bruno, Eichmann Anne, Simons Michael
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.
Cell Mol Life Sci. 2013 Sep 28;71(5):867-83. doi: 10.1007/s00018-013-1475-1.
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.
动静脉畸形是由于血管模式异常导致血液从动脉流向静脉而没有中间的毛细血管床。最近的研究揭示了Notch和TGF-β信号通路在血管模式形成中的重要性。具体而言，Notch信号在动脉特化和分支抑制中发挥着越来越明显的作用，而TGF-β则与血管平滑肌在血管生成刺激下的发育和重塑有关。因此，这些生理作用使这两条通路都与动静脉畸形的发病机制有关。在本综述中，我们总结了有助于动静脉畸形形成的内皮信号研究以及与其发病机制相关基因的作用。我们还将进一步讨论内皮信号如何促进血管平滑肌发育，以及信号通路的知识如何为这些血管病变的医学治疗提供靶点。
