BMPR2型
前列环素
肺动脉高压
胚胎血管重塑
缺氧(环境)
医学
骨形态发生蛋白
内科学
药理学
生物信息学
生物
化学
基因
生物化学
有机化学
氧气
作者
Alexander J. Ainscough,T. Jarrod Smith,Maike Haensel,Christopher J. Rhodes,Adam Fellows,Harry J. Whitwell,Eleni Vasilaki,Kelly Gray,Adrian Freeman,Luke Howard,John Wharton,Benjamin J. Dunmore,Paul D. Upton,Martin R. Wilkins,Joshua B. Edel,Beata Wójciak‐Stothard
标识
DOI:10.1038/s42003-022-04169-z
摘要
Pulmonary arterial hypertension (PAH) is an unmet clinical need. The lack of models of human disease is a key obstacle to drug development. We present a biomimetic model of pulmonary arterial endothelial-smooth muscle cell interactions in PAH, combining natural and induced bone morphogenetic protein receptor 2 (BMPR2) dysfunction with hypoxia to induce smooth muscle activation and proliferation, which is responsive to drug treatment. BMPR2- and oxygenation-specific changes in endothelial and smooth muscle gene expression, consistent with observations made in genomic and biochemical studies of PAH, enable insights into underlying disease pathways and mechanisms of drug response. The model captures key changes in the pulmonary endothelial phenotype that are essential for the induction of SMC remodelling, including a BMPR2-SOX17-prostacyclin signalling axis and offers an easily accessible approach for researchers to study pulmonary vascular remodelling and advance drug development in PAH.
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