Pulmonary hypertension (PH) observed during respiratory syncytial virus (RSV) bronchiolitis is associated with morbidity and mortality, especially in children with congenital heart disease. Yet, the pathophysiological mechanisms of RSV-associated PH remain unclear. Therefore, this study aimed to investigate the pathophysiological mechanism of RSV-associated PH. We employed a translational mouse model of RSV-associated PH, in which wild-type (WT) and ST2 knockout neonatal mice were infected with RSV at 5-days old and reinfected 4-weeks later. The development of PH in WT mice following RSV reinfection was evidenced by elevated right ventricle systolic pressure, shortenedpulmonary artery acceleration time (PAT) and decreased PAT/ejection time (ET) ratio. It coincided with the augmentation of periostin and IL-13 expression, and increased arginase bioactivity by both arginase 1 and 2 as well as induction of nitric oxide synthase (NOS) uncoupling. The absence of ST2 signaling prevented RSV reinfected mice from developing PH by suppressing NOS uncoupling. In summary, ST2 signaling was involved in the development of RSV-associated PH. ST2 signaling inhibition may be a novel therapeutic target for RSV-associated PH.

中文翻译：

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ST2 信号传导的缺乏可改善 RSV 相关的肺动脉高压

在呼吸道合胞病毒 (RSV) 细支气管炎期间观察到的肺动脉高压 (PH) 与发病率和死亡率相关，尤其是在患有先天性心脏病的儿童中。然而，RSV 相关 PH 的病理生理机制仍不清楚。因此，本研究旨在探讨 RSV 相关 PH 的病理生理机制。我们采用了 RSV 相关 PH 的转化小鼠模型，其中野生型 (WT) 和 ST2 敲除新生小鼠在 5 天大时感染 RSV，并在 4 周后再次感染。RSV 再感染后 WT 小鼠 PH 的发展通过右心室收缩压升高、肺动脉加速时间 (PAT) 缩短和 PAT/射血时间 (ET) 比率降低来证明。它与骨膜素和 IL-13 表达的增加相吻合，精氨酸酶 1 和 2 以及一氧化氮合酶 (NOS) 解偶联的诱导增加了精氨酸酶的生物活性。ST2 信号传导的缺失通过抑制 NOS 解偶联来阻止 RSV 再感染小鼠发展为 PH。总之，ST2 信号传导参与了 RSV 相关 PH 的发展。ST2 信号传导抑制可能是 RSV 相关 PH 的新治疗靶点。