Biosanté Unit U1292, Grenoble Alpes University, INSERM, CEA, Grenoble, France.
Hospices Civils de Lyon, National HHT Reference Center and Genetics Department, Femme-Mère-Enfants Hospital, Bron, France.
J Clin Invest. 2024 Feb 15;134(4):e176379. doi: 10.1172/JCI176379.
Hereditary hemorrhagic telangiectsia (HHT) is an inherited vascular disorder with highly variable expressivity, affecting up to 1 in 5,000 individuals. This disease is characterized by small arteriovenous malformations (AVMs) in mucocutaneous areas (telangiectases) and larger visceral AVMs in the lungs, liver, and brain. HHT is caused by loss-of-function mutations in the BMP9-10/ENG/ALK1/SMAD4 signaling pathway. This Review presents up-to-date insights on this mutated signaling pathway and its crosstalk with proangiogenic pathways, in particular the VEGF pathway, that has allowed the repurposing of new drugs for HHT treatment. However, despite the substantial benefits of these new treatments in terms of alleviating symptom severity, this not-so-uncommon bleeding disorder still currently lacks any FDA- or European Medicines Agency-approved (EMA-approved) therapies.
遗传性出血性毛细血管扩张症（HHT）是一种具有高度变异性表达的遗传性血管疾病，影响多达每 5000 人中的 1 人。这种疾病的特征是在粘膜皮肤区域（毛细血管扩张症）存在小的动静脉畸形（AVM）和肺部、肝脏和大脑中的较大内脏 AVM。HHT 是由 BMP9-10/ENG/ALK1/SMAD4 信号通路中的功能丧失突变引起的。本综述介绍了该突变信号通路及其与促血管生成途径（特别是 VEGF 途径）的最新见解，这使得新药物可用于 HHT 的治疗。然而，尽管这些新疗法在缓解症状严重程度方面具有显著益处，但这种并非罕见的出血性疾病目前仍然缺乏任何美国食品药品监督管理局（FDA）或欧洲药品管理局（EMA）批准的治疗方法。
