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靶向可溶性转化生长因子-β因子:肺动脉高压精准治疗的进展

Targeting Soluble TGF-β Factors: Advances in Precision Therapy for Pulmonary Arterial Hypertension.

作者信息

Becher Clarissa, Wits Marius, de Man Frances S, Sanchez-Duffhues Gonzalo, Goumans Marie-Jose

机构信息

Department of Cell and Chemical Biology, Leiden University Medical Center (LUMC), Leiden, the Netherlands.

Department of Pulmonary Medicine, Amsterdam University Medical Center, Vrije Universiteit, Amsterdam, the Netherlands.

出版信息

JACC Basic Transl Sci. 2024 Jun 19;9(11):1360-1374. doi: 10.1016/j.jacbts.2024.04.005. eCollection 2024 Nov.

Abstract

Pulmonary arterial hypertension (PAH) is a rare progressive disease characterized by pulmonary artery vascular remodeling, increased vascular resistance, and subsequent right ventricular hypertrophy and right heart failure. It is triggered by disrupted transforming growth factor (TGF)-β signaling, including loss-of-function mutations in the bone morphogenetic protein (BMP) receptor 2. Emerging treatments aim to inhibit elevated TGF-β levels or enhance diminished endothelial BMP signaling. This review aims to summarize the role of the TGF-β superfamily in the pathobiology of PAH and recent discoveries highlighting altered expression of TGF-β-related soluble factors in PAH patients that can serve as potential biomarkers and drug targets. The discussion focuses on how these altered factors can guide treatment decisions and monitor therapeutic responses, facilitating personalized patient care through the integration of diagnostics and therapy, that is, precision medicine. This approach tailors treatment strategies to individual patients based on their unique disease characteristics.

摘要

肺动脉高压(PAH)是一种罕见的进行性疾病,其特征为肺动脉血管重塑、血管阻力增加,以及随后出现的右心室肥厚和右心衰竭。它由转化生长因子(TGF)-β信号通路紊乱引发,包括骨形态发生蛋白(BMP)受体2的功能丧失突变。新兴治疗方法旨在抑制升高的TGF-β水平或增强减弱的内皮BMP信号传导。本综述旨在总结TGF-β超家族在PAH病理生物学中的作用,以及近期的发现,这些发现突出了PAH患者中TGF-β相关可溶性因子表达的改变,这些因子可作为潜在的生物标志物和药物靶点。讨论重点在于这些改变的因子如何指导治疗决策和监测治疗反应,通过整合诊断和治疗,即精准医学,促进个性化患者护理。这种方法根据个体患者独特的疾病特征量身定制治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a305/11604486/ea44418fc53a/ga1.jpg

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