Bartoli Carlo R, Hennessy-Strahs Samson, Dowling Robert D, Gaynor J William, Glatz Andrew C
Division of Cardiovascular Surgery, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Department of Cardiothoracic Surgery, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
JACC Basic Transl Sci. 2021 Mar 22;6(3):222-235. doi: 10.1016/j.jacbts.2020.12.014. eCollection 2021 Mar.
Children with a bidirectional superior cavopulmonary (Glenn) circulation develop angiodysplasia and pulmonary arteriovenous malformations (AVMs). The von Willebrand factor (vWF)-angiopoietin axis plays a major role in AVM formation in multiple diseases. We observed derangements in global angiogenic signaling, vWF metabolism, angiopoietins, and in vitro angiogenesis in children with a Glenn circulation versus controls and within Glenn pulmonary versus systemic circulations. These findings support the novel hypothesis that abnormalities in the vWF-angiopoietin axis may dysregulate angiogenesis and contribute to Glenn pulmonary AVMs. The vWF-angiopoietin axis may be a target to correct angiogenic imbalance in Glenn patients, for whom no targeted therapy exists.
患有双向上腔静脉-肺动脉（格林）循环的儿童会发展出血管发育异常和肺动静脉畸形（AVM）。血管性血友病因子（vWF）-血管生成素轴在多种疾病的AVM形成中起主要作用。我们观察到，与对照组相比，患有格林循环的儿童以及格林肺循环与体循环内的儿童在整体血管生成信号、vWF代谢、血管生成素和体外血管生成方面存在紊乱。这些发现支持了这一新假说，即vWF-血管生成素轴的异常可能会失调血管生成并导致格林肺AVM。vWF-血管生成素轴可能是纠正格林患者血管生成失衡的一个靶点，目前尚无针对格林患者的靶向治疗方法。
