Abdelilah-Seyfried Salim
J Clin Invest. 2024 Aug 1;134(15):e182904. doi: 10.1172/JCI182904.
Cerebral arteriovenous malformations represent the most common form of vascular malformations and can cause recurrent bleeding and hemorrhagic stroke. The current issue of the JCI features an article by Zhao et al. describing a mouse model of cerebral arteriovenous malformations. Endothelial cells lacking matrix Gla protein, a BMP inhibitor, underwent epigenetic changes characteristic of an endothelial-to-mesenchymal fate transition. The authors uncovered a two-step process for this transition controlled by the epigenetic regulator histone deacetylase 2 (HDAC2), which controls endothelial cell differentiation, and by enhancer of zeste homolog 1 (EZH1), which suppressed mesenchymal fate. This discovery provides a promising entry point for preventive pharmacological interventions.
脑动静脉畸形是最常见的血管畸形形式，可导致反复出血和出血性中风。本期《临床研究杂志》刊登了赵等人撰写的一篇文章，描述了一种脑动静脉畸形的小鼠模型。缺乏基质Gla蛋白（一种骨形态发生蛋白抑制剂）的内皮细胞发生了内皮向间充质命运转变所特有的表观遗传变化。作者发现了这一转变的两步过程，该过程由控制内皮细胞分化的表观遗传调节因子组蛋白去乙酰化酶2（HDAC2）和抑制间充质命运的zeste同源物1增强子（EZH1）控制。这一发现为预防性药物干预提供了一个有前景的切入点。
