Deciphering the role of BMP9-BMP10 and YAP-TEAD signaling in vascular smooth muscle heterogeneity and pulmonary hypertension (A02)

BMP9和BMP10结合ALK1受体，与肺动脉高压（PH）有关。我们发现，小鼠BMP9/10基因失活导致血管张力和血管平滑肌细胞（VSMC）的急剧变化，从而保护小鼠免受缺氧诱导的ph。这些作用是由VSMC中Alk受体的血管床特异性表达介导的。我们将阐明BMP9/BMP10/Alk1轴对肺动脉反向重塑的影响，分析alk受体异质表达在VSMCs中的意义，探讨Alk1/Smad1/5/8与YAP-TEAD信号之间的串话，阐明BMP9/10依赖性差异剪接在VSMCs中的影响。

BMP9 and BMP10 bind to the ALK1 receptor, which is linked to pulmonary hypertension (PH). We found that genetic inactivation of BMP9/10 in mice causes dramatic changes in vascular tone and diminution of vascular smooth muscle cells (VSMC), protecting mice from hypoxia-induced PH. These effects are mediated by vascular bed-specific expression of Alk receptors in VSMC. We will elucidate the impact of the BMP9/BMP10/Alk1 axis on reverse remodeling of pulmonary arteries, analyze the meaning of heterogeneous Alk-receptor expression in VSMCs, explore the cross-talk between Alk1/Smad1/5/8 and YAP-TEAD signaling and elucidate the impact of BMP9/10 dependent differential splicing in VSMCs.