Lung transcriptomes of wild type, β-arrestin 1 -/-, and β-arrestin 2 -/- mice exposed to normoxia or chronic hypoxia. Lung transcriptomes of wild type, β-arrestin 1 -/-, and β-arrestin 2 -/- mice exposed to normoxia or chronic hypoxia

We found that β-arrestin 1 -/- mice were more sensitive to hypoxia-induced pulmonary arterial hypertension with increased right ventricle hypertrophy and higher right ventricle systolic pressure, while β-arrestin 2 -/- mice developed right ventricle hypertrophy comparable to wild type mice. Moreover, β-arrestin 1 -/- mice had worse right ventricle function than wild type mice in response to chronic hypoxia, whereas β-arrestin 2 -/- mice relatively preserved right ventricle function compared to wild type mice. To investigate the molecular mechanisms responsible for the worse PAH in β-arrestin 1 -/- mice, we performed lung transcriptome analysis of wild type, β-arrestin 1 -/-, and β-arrestin 2 -/- mice using high-throughput RNA-seq. Overall design: Deep sequencing of lung transcriptomes from wild type, β-arrestin 1 -/-, and β-arrestin 2 -/- mice exposed to normoxia or chronic hypoxia in triplicate.

我们发现，β抑制蛋白1纯合敲除（β-arrestin 1⁻/⁻）小鼠对低氧诱导的肺动脉高压更为敏感，表现为右心室肥厚程度加重、右心室收缩压升高；而β抑制蛋白2纯合敲除（β-arrestin 2⁻/⁻）小鼠的右心室肥厚程度与野生型小鼠相当。此外，相较于野生型小鼠，β抑制蛋白1⁻/⁻小鼠在慢性低氧刺激下的右心室功能受损更为严重；而β抑制蛋白2⁻/⁻小鼠的右心室功能则相对保留。为探究β抑制蛋白1⁻/⁻小鼠肺动脉高压（PAH）症状更严重的分子机制，我们采用高通量RNA测序（RNA-seq）技术，对野生型、β抑制蛋白1⁻/⁻及β抑制蛋白2⁻/⁻小鼠开展肺转录组分析。整体实验设计：对暴露于常氧或慢性低氧环境下的野生型、β抑制蛋白1⁻/⁻及β抑制蛋白2⁻/⁻小鼠的肺转录组进行深度测序，每组设置3次生物学重复。